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Jiao W, Zhao L, Mei J, Zhong J, Yu Y, Bi N, Zhang L, Wang L, Fu X, Wang J, Lu S, Liu L, Gao S. Clinical practice guidelines for perioperative multimodality treatment of non-small cell lung cancer. Chin Med J (Engl) 2025:00029330-990000000-01521. [PMID: 40246578 DOI: 10.1097/cm9.0000000000003635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment. METHODS The working group consisted of 91 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process. RESULTS The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendation were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC. CONCLUSIONS This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
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Affiliation(s)
- Wenjie Jiao
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, China
| | - Liang Zhao
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jiandong Mei
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jia Zhong
- CAMS Key Laboratory of Translational Research on Lung Cancer, State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yongfeng Yu
- Department of Medical Oncology, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Nan Bi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China
| | - Lan Zhang
- Psychological Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Lvhua Wang
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong 518117, China
| | - Xiaolong Fu
- Department of Radiation Oncology, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Jie Wang
- CAMS Key Laboratory of Translational Research on Lung Cancer, State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Shun Lu
- Department of Medical Oncology, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Lunxu Liu
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Shugeng Gao
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Ma Z, Fu F, Zhang Y, Chen H. Long-term outcomes of neoadjuvant gefitinib in resectable stage II-IIIA non-small cell lung cancer: A phase II, prospective cohort study. Lung Cancer 2025; 201:108457. [PMID: 39999636 DOI: 10.1016/j.lungcan.2025.108457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 02/09/2025] [Accepted: 02/19/2025] [Indexed: 02/27/2025]
Abstract
BACKGROUND Our previous study has showed the safety and efficacy of preoperative gefitinib in patients with stage II-IIIA resectable non-small cell lung cancer (NSCLC). This study aimed to report the long-term survival analysis and recurrent patterns. METHODS This was a single-arm, phase II clinical trial. Patients with resectable stage II-IIIA NSCLC harboring EGFR exon 19 deletion or exon 21 L858R mutations were enrolled. Patients were administrated with preoperative gefitinib (250 mg once daily for 42 days), followed by surgical resection. The primary endpoint was objective response rate (ORR); secondary endpoints included the rate of major pathologic response (MPR), disease-free survival (DFS), overall survival (OS). MPR was defined as the presence of no more than 10 % viable tumor. Chi-square test was used to assess the differences in CNS recurrence rates and recurrent patterns. RESULTS Of the 33 intention-to-treat patients, ORR was 54.5 % (95 % confidence interval (CI), 37.7-70.7), and the rate of MPR was 24.2 % (95 % CI, 11.9-40.4). Among the investigated 28 patients, the median follow-up was 108.5 months. The median OS was 89.8 months (95 % CI, 44.37-NC), and the median DFS was 36.4 months (95 % CI, 18.9-NC). In addition, MPR continued to indicate significantly improved DFS, as well as OS (DFS, p = 0.015; OS, p = 0.037). The neoadjuvant gefitinib group showed prolonged DFS and OS than platinum doublet group (hazard ratio (HR) = 1.71, 95 % CI, 1.02-2.85, p = 0.038; and HR = 2.31; 95 % CI, 1.28-4.16, p = 0.0044, respectively). There was a significant difference in the distant recurrence patterns between the two groups (p = 0.032). Moreover, the gefitinib group showed similar overall brain metastasis rate than platinum doublet group (21.4 % versus 27.5 %). CONCLUSIONS With satisfying prognosis benefits and acceptable brain metastasis rate in long-term follow-up, gefitinib exhibited clinical viability for operable stage II-IIIA EGFR-mutant NSCLC over chemotherapy in the neoadjuvant setting. MPR was significantly associated with both prolonged DFS and OS, manifesting its potential as an essential endpoint for future neoadjuvant trials.
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Affiliation(s)
- Zhanming Ma
- Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Fangqiu Fu
- Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Yang Zhang
- Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
| | - Haiquan Chen
- Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
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Fuorivia V, Attili I, Corvaja C, Asnaghi R, Carnevale Schianca A, Trillo Aliaga P, Del Signore E, Spitaleri G, Passaro A, de Marinis F. Management of Non-Metastatic Non-Small Cell Lung Cancer (NSCLC) with Driver Gene Alterations: An Evolving Scenario. Curr Oncol 2024; 31:5121-5139. [PMID: 39330007 PMCID: PMC11431721 DOI: 10.3390/curroncol31090379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 08/21/2024] [Accepted: 08/28/2024] [Indexed: 09/28/2024] Open
Abstract
The ever-growing knowledge regarding NSCLC molecular biology has brought innovative therapies into clinical practice; however, the treatment situation in the non-metastatic setting is rapidly evolving. Indeed, immunotherapy-based perioperative treatments are currently considered the standard of care for patients with resectable NSCLC in the absence of EGFR mutations or ALK gene rearrangements. Recently, data have been presented on the use of tyrosine kinase inhibitors (TKIs) in the adjuvant and locally advanced setting for patients with NSCLC harboring such driver gene alterations. The aim of the current work is to review the available evidence on the use of targeted treatments in the non-metastatic setting, together with a summary of the ongoing trials designed for actionable gene alterations other than EGFR and ALK. To date, 3-year adjuvant osimertinib treatment has been demonstrated to improve DFS and OS and to reduce CNS recurrence in resected EGFR-mutated NSCLC in stage IB-IIIA (TNM 7th edition). The use of osimertinib after chemo-radiation in stage III unresectable EGFR-mutated NSCLC showed the relevant PFS improvement. In the ALK-positive setting, 2-year alectinib treatment was shown to clearly improve DFS compared to adjuvant standard chemotherapy in resected NSCLC with stage IB (≥4 cm)-IIIA (TNM 7th edition). Several trials are ongoing to establish the optimal adjuvant TKI treatment duration, as well as neoadjuvant TKI strategies in EGFR- and ALK-positive disease, and (neo)adjuvant targeted treatments in patients with actionable gene alterations other than EGFR or ALK. In conclusion, our review depicts how the current treatment scenario is expected to rapidly change in the context of non-metastatic NSCLC with actionable gene alterations, hence appropriate molecular testing from the early stages has become crucial to establish the most adequate approaches both in the perioperative and the locally advanced disease.
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Affiliation(s)
- Valeria Fuorivia
- Division of Thoracic Oncology, European Institute of Oncology IRCCS, 20141 Milan, Italy
| | - Ilaria Attili
- Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy (A.P.)
| | - Carla Corvaja
- Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy (A.P.)
| | - Riccardo Asnaghi
- Division of Thoracic Oncology, European Institute of Oncology IRCCS, 20141 Milan, Italy
| | | | - Pamela Trillo Aliaga
- Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy (A.P.)
| | - Ester Del Signore
- Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy (A.P.)
| | - Gianluca Spitaleri
- Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy (A.P.)
| | - Antonio Passaro
- Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy (A.P.)
| | - Filippo de Marinis
- Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy (A.P.)
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Shao W, Liu Z, Li B, Chen F, Liu J, Li H, Guo H. Neoadjuvant targeted therapy versus targeted combined with chemotherapy for resectable EGFR-mutant non-small cell lung cancer: a retrospective controlled real-world study. Front Oncol 2024; 14:1349300. [PMID: 39081712 PMCID: PMC11286491 DOI: 10.3389/fonc.2024.1349300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 06/28/2024] [Indexed: 08/02/2024] Open
Abstract
Background This study aimed to assess the role and effect of neoadjuvant targeted therapy (TT) versus targeted combined with chemotherapy (TC) for resectable EGFR-mutant non-small cell lung cancer (NSCLC). Methods Between March 2021 and June 2023, 20 patients with stage IA3-IIIB NSCLC were enrolled in the study. Eleven patients received EGFR-TKIs in the TT group, while nine patients received EGFR-TKIs and two cycles of cisplatin-based doublet chemotherapy (TC group). We compare the differences between the two groups through the following variables, including age, sex, surgical approach, postoperative complications, neoadjuvant therapy adverse events, complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), major pathologic response (MPR), and pathologic complete response (pCR). Results Patients were predominantly female (75%) and never-smokers (95%). The average age was 59.2 years (range 46-79 years). Fifty-five percent harbored an exon 19 EGFR mutation and 45% an exon 21 mutation. The average targeted drug dosing time was 2.91 ± 1.7 (range 1-6) months in the TT group and 3.56 ± 3.54 (range 1-12) months in the TC group (P=0.598). The most common side effects were rash and diarrhea. No grade 5 events with neoadjuvant therapy were observed. The rate of R0 resection was 100% in all patients. Among the 11 patients in the TT group, 6 achieved a PR and 5 had SD, resulting in an ORR of 54.5%. Among the 9 patients in the TC group, 6 had PR and the remaining 3 had SD, resulting in an ORR of 66.6%. one patient (11.1%) in the TC group achieved pCR, while no patients in the TT group achieved pCR (P = 0.142). Two patients (18.2%) in the TT group reached MPR, and 2 patients (22.2%) in the TC group reached MPR (P = 0.257). The overall clinical downstage rate is 60%. Only 9 (45%) cases of yield clinical TNM (ycTNM) were consistent with yield pathologic TNM (ypTNM). Conclusion Results from this retrospective controlled research indicate that the neoadjuvant TT group is likely to be more effective outcomes and has safer profile in patients with EGFR-positive NSCLC than the neoadjuvant TC group. However, our results need to be validated in a multicenter, large sample prospective study.
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Affiliation(s)
| | | | | | | | | | | | - Hongbo Guo
- Department of Thoracic Surgical Ward II, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
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Peng SONG, Yong CUI. [Progress and Discussion of Perioperative Targeted Therapy in Patients
with EGFR-mutated Resectable Non-small Cell Lung Cancer]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2024; 27:383-390. [PMID: 38880926 PMCID: PMC11183319 DOI: 10.3779/j.issn.1009-3419.2024.106.11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Indexed: 06/18/2024]
Abstract
Lung cancer is still the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer, accounting for about 80%. Approximately 30% of all patients with NSCLC have resectable early and middle stage disease at the time of diagnosis. Recently, the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have made a major breakthrough in the adjuvant targeted therapy of EGFR-mutated resectable NSCLC, and are recommended by the guidelines for clinical use. In this review, we summarize the clinical research progress of perioperative adjuvant targeted therapy for EGFR-mutated resectable NSCLC, and discuss the key issues in the clinical researches.
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Sorin M, Prosty C, Ghaleb L, Nie K, Katergi K, Shahzad MH, Dubé LR, Atallah A, Swaby A, Dankner M, Crump T, Walsh LA, Fiset PO, Sepesi B, Forde PM, Cascone T, Provencio M, Spicer JD. Neoadjuvant Chemoimmunotherapy for NSCLC: A Systematic Review and Meta-Analysis. JAMA Oncol 2024; 10:621-633. [PMID: 38512301 PMCID: PMC10958389 DOI: 10.1001/jamaoncol.2024.0057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 11/03/2023] [Indexed: 03/22/2024]
Abstract
Importance To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%. Objective To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials. Data Sources MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of neoadjuvant chemoimmunotherapy and chemotherapy that included at least 10 patients. Study Selection Observational studies and trials reporting the use of neoadjuvant radiotherapy, including chemoradiotherapy, molecular targeted therapy, or immunotherapy monotherapy, were excluded. Main Outcomes and Measures Surgical, pathological, and efficacy end points and adverse events were pooled using a random-effects meta-analysis. Results Among 43 eligible trials comprising 5431 patients (4020 males [74.0%]; median age range, 55-70 years), there were 8 randomized clinical trials with 3387 patients. For randomized clinical trials, pooled overall survival (hazard ratio, 0.65; 95% CI, 0.54-0.79; I2 = 0%), event-free survival (hazard ratio, 0.59; 95% CI, 0.52-0.67; I2 = 14.9%), major pathological response (risk ratio, 3.42; 95% CI, 2.83-4.15; I2 = 31.2%), and complete pathological response (risk ratio, 5.52; 95% CI, 4.25-7.15; I2 = 27.4%) favored neoadjuvant chemoimmunotherapy over neoadjuvant chemotherapy. For patients with baseline tumor PD-L1 levels less than 1%, there was a significant benefit in event-free survival for neoadjuvant chemoimmunotherapy compared with chemotherapy (hazard ratio, 0.74; 95% CI, 0.62-0.89; I2 = 0%). Conclusion and Relevance This study found that neoadjuvant chemoimmunotherapy was superior to neoadjuvant chemotherapy across surgical, pathological, and efficacy outcomes. These findings suggest that patients with resectable NSCLC with tumor PD-L1 levels less than 1% may have an event-free survival benefit with neoadjuvant chemoimmunotherapy.
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Affiliation(s)
- Mark Sorin
- Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, Quebec, Canada
- Department of Human Genetics, McGill University, Montréal, Quebec, Canada
- Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
| | - Connor Prosty
- Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
| | - Louis Ghaleb
- Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
| | - Kathy Nie
- Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
| | - Khaled Katergi
- Faculty of Medicine, University of Montreal, Montréal, Quebec, Canada
| | - Muhammad H. Shahzad
- Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
| | - Laurie-Rose Dubé
- Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
| | - Aline Atallah
- Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, Quebec, Canada
- Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
| | - Anikka Swaby
- Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, Quebec, Canada
- Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
| | - Matthew Dankner
- Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, Quebec, Canada
- Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada
| | - Trafford Crump
- Department of Surgery, McGill University, Montréal, Quebec, Canada
| | - Logan A. Walsh
- Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, Quebec, Canada
- Department of Human Genetics, McGill University, Montréal, Quebec, Canada
| | - Pierre O. Fiset
- Department of Pathology, McGill University, Montréal, Quebec, Canada
| | - Boris Sepesi
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Patrick M. Forde
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland
| | - Tina Cascone
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Mariano Provencio
- Department of Medical Oncology, Puerta de Hierro University Hospital, Autonomous University, Madrid, Instituto de Investigacion Sanitaria Puerta de Hierro–Segovia de Arana, Spain
| | - Jonathan D. Spicer
- Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, Quebec, Canada
- Department of Surgery, McGill University, Montréal, Quebec, Canada
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Liu B, Liu X, Xing H, Ma H, Lv Z, Zheng Y, Xing W. A new, potential and safe neoadjuvant therapy strategy in epidermal growth factor receptor mutation-positive resectable non-small-cell lung cancer-targeted therapy: a retrospective study. Front Oncol 2024; 14:1349172. [PMID: 38414743 PMCID: PMC10897038 DOI: 10.3389/fonc.2024.1349172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 01/29/2024] [Indexed: 02/29/2024] Open
Abstract
Background Studies of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resectable non-small-cell lung cancer (NSCLC) have been conducted. The purpose of our study was to evaluate the benefits of osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC. Method This retrospective study evaluated patients with EGFR mutations in exon 19 or 21 who received targeted therapy with osimertinib (80 mg per day) before surgery between January 2019 and October 2023 in Henan Cancer Hospital. Results Twenty patients were evaluated, all of whom underwent surgery. The rate of R0 resection was 100% (20/20). The objective response rate was 80% (16/20), and the disease control rate was 95% (19/20). Postoperative pathological analysis showed a 25% (5/20) major pathological response rate and 15% (3/20) pathological complete response rate. In total, 25% (5/20) developed adverse events (AEs), and the rate of grades 3-4 AEs was 10% (2/20). One patient experienced a grade 3 skin rash, and 1 patient experienced grade 3 diarrhea. Conclusion Osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC is safe and well tolerated. Osimertinib has the potential to improve the radical resection rate and prognosis.
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Affiliation(s)
- Baoxing Liu
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Xingyu Liu
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Huifang Xing
- Department of Geriatric Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Haibo Ma
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Zhenyu Lv
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Yan Zheng
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Wenqun Xing
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
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Ahn BC, Park C, Kim MS, Lee JM, Choi JH, Kim HY, Lee GK, Yu N, Lee Y, Han JY. Tumor Microenvironment Modulation by Neoadjuvant Erlotinib Therapy and Its Clinical Impact on Operable EGFR-Mutant Non-Small Cell Lung Cancer. Cancer Res Treat 2024; 56:70-80. [PMID: 37340841 PMCID: PMC10789966 DOI: 10.4143/crt.2023.482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 06/20/2023] [Indexed: 06/22/2023] Open
Abstract
PURPOSE Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have greatly improved survival in EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC); however, their effects on the tumor microenvironment (TME) are unknown. We assessed the changes induced by neoadjuvant erlotinib therapy (NE) in the TME of operable EGFRm NSCLC. MATERIALS AND METHODS This was a single-arm phase II trial for neoadjuvant/adjuvant erlotinib therapy in patients with stage II/IIIA EGFRm NSCLC (EGFR exon 19 deletion or L858R mutations). Patients received up to 2 cycles of NE (150 mg/day) for 4 weeks, followed by surgery and adjuvant erlotinib or vinorelbine plus cisplatin therapy depending on observed NE response. TME changes were assessed based on gene expression analysis and mutation profiling. RESULTS A total of 26 patients were enrolled; the median age was 61, 69% were female, 88% were stage IIIA, and 62% had L858R mutation. Among 25 patients who received NE, the objective response rate was 72% (95% confidence interval [CI], 52.4 to 85.7). The median disease-free and overall survival (OS) were 17.9 (95% CI, 10.5 to 25.4) and 84.7 months (95% CI, 49.7 to 119.8), respectively. Gene set enrichment analysis in resected tissues revealed upregulation of interleukin, complement, cytokine, transforming growth factor β, and hedgehog pathways. Patients with upregulated pathogen defense, interleukins, and T-cell function pathways at baseline exhibited partial response to NE and longer OS. Patients with upregulated cell cycle pathways at baseline exhibited stable/progressive disease after NE and shorter OS. CONCLUSION NE modulated the TME in EGFRm NSCLC. Upregulation of immune-related pathways was associated with better outcomes.
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Affiliation(s)
- Beung-Chul Ahn
- Center for Lung Cancer, Division of Hematology and Oncology, Department of Internal Medicine, Research Institute and Hospital, National Cancer Center, Goyang,
Korea
| | - Charny Park
- Research Institute, National Cancer Center, Goyang,
Korea
| | - Moon Soo Kim
- Center for Lung Cancer, Department of Thoracic Surgery, Research Institute and Hospital, National Cancer Center, Goyang,
Korea
| | - Jong Mog Lee
- Center for Lung Cancer, Department of Thoracic Surgery, Research Institute and Hospital, National Cancer Center, Goyang,
Korea
| | - Jin Ho Choi
- Center for Lung Cancer, Department of Thoracic Surgery, Research Institute and Hospital, National Cancer Center, Goyang,
Korea
| | - Hyae Young Kim
- Department of Radiology, Research Institute and Hospital, National Cancer Center, Goyang,
Korea
| | - Geon Kook Lee
- Department of Pathology, Research Institute and Hospital, National Cancer Center, Goyang,
Korea
| | - Namhee Yu
- Research Institute, National Cancer Center, Goyang,
Korea
| | - Youngjoo Lee
- Center for Lung Cancer, Division of Hematology and Oncology, Department of Internal Medicine, Research Institute and Hospital, National Cancer Center, Goyang,
Korea
| | - Ji-Youn Han
- Center for Lung Cancer, Division of Hematology and Oncology, Department of Internal Medicine, Research Institute and Hospital, National Cancer Center, Goyang,
Korea
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Kang K, Jiang Z, Kai J, Chen S, Xiong F. Almonertinib as a neoadjuvant therapy for patients with a superior pulmonary sulcus tumor with activated EGFR mutation: A case report. Exp Ther Med 2023; 26:564. [PMID: 37954117 PMCID: PMC10632965 DOI: 10.3892/etm.2023.12263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 08/23/2023] [Indexed: 11/14/2023] Open
Abstract
A superior pulmonary sulcus tumor, also known as a Pancoast tumor, invades tissues or organs at the entrance of the thorax, such as the brachial plexus, upper ribs, vertebrae, subclavian vessels and stellate ganglia. Induction concurrent chemoradiotherapy followed by radical surgical resection is the preferred treatment. The present study reported the case of a 52-year-old male who presented at Hubei Cancer Hospital, Tongji Medical College (Wuhan, Hubei) with left chest pain and an abnormal chest computed tomography scan showing a mass of 81x43 mm in the left upper chest wall that invaded the first, second and third anterior ribs. Biopsy of the mass showed stage cT4N0M0, IIIA, poorly differentiated adenocarcinoma and epidermal growth factor receptor+. The patient was treated by induction chemotherapy and targeted therapy, which was followed by surgical resection of the left upper lobe and the affected chest wall via the transmanubrial approach. The targeted therapy with almonertinib was continued postoperatively. To date, no disease recurrence has been detected during the 4 months follow-up.
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Affiliation(s)
- Kai Kang
- Department of Thoracic Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, P.R. China
| | - Zhixiao Jiang
- Department of Thoracic Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, P.R. China
| | - Jindan Kai
- Department of Thoracic Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, P.R. China
| | - Si Chen
- Department of Thoracic Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, P.R. China
| | - Fei Xiong
- Department of Thoracic Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, P.R. China
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10
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Lee JM, McNamee CJ, Toloza E, Negrao MV, Lin J, Shum E, Cummings AL, Kris MG, Sepesi B, Bara I, Kurtsikidze N, Schulze K, Ngiam C, Chaft JE. Neoadjuvant Targeted Therapy in Resectable NSCLC: Current and Future Perspectives. J Thorac Oncol 2023; 18:1458-1477. [PMID: 37451404 PMCID: PMC11040203 DOI: 10.1016/j.jtho.2023.07.006] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 06/20/2023] [Accepted: 07/06/2023] [Indexed: 07/18/2023]
Abstract
The standard of care (SoC) for medically operable patients with early-stage (stages I-IIIB) NSCLC is surgery combined with (neo)adjuvant systemic therapy for patients with stages II to IIIB disease and some stage IB or, rarely, chemoradiation (stage III disease with mediastinal lymph node metastases). Despite these treatments, metastatic recurrence is common and associated with poor survival, highlighting the need for systemic therapies that are more effective than the current SoC. After the success of targeted therapy (TT) in patients with advanced NSCLC harboring oncogenic drivers, these agents are being investigated for the perioperative (neoadjuvant and adjuvant) treatment of patients with early-stage NSCLC. Adjuvant osimertinib is the only TT approved for use in the early-stage setting, and there are no approved neoadjuvant TTs. We discuss the importance of comprehensive biomarker testing at diagnosis to identify individuals who may benefit from neoadjuvant targeted treatments and review emerging data from neoadjuvant TT trials. We also address the potential challenges for establishing neoadjuvant TTs as SoC in the early-stage setting, including the identification and validation of early response markers to guide care and accelerate drug development, and discuss safety considerations in the perioperative setting. Initial data indicate that neoadjuvant TTs are effective and well tolerated in patients with EGFR- or ALK-positive early-stage NSCLC. Data from ongoing trials will determine whether neoadjuvant targeted agents will become a new SoC for individuals with oncogene-addicted resectable NSCLC.
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Affiliation(s)
- Jay M Lee
- Division of Thoracic Surgery, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
| | - Ciaran J McNamee
- Department of Surgery, Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Eric Toloza
- Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida; Department of Surgery and Department of Oncologic Sciences, University of South Florida Health Morsani College of Medicine, Tampa, Florida
| | - Marcelo V Negrao
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jules Lin
- Section of Thoracic Surgery, University of Michigan Rogel Cancer Center, Ann Arbor, Michigan
| | - Elaine Shum
- Division of Hematology and Medical Oncology, Department of Medicine, Perlmutter Cancer Center at NYU Langone Health, New York, New York
| | - Amy L Cummings
- Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California
| | - Mark G Kris
- Thoracic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, New York
| | - Boris Sepesi
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ilze Bara
- US Medical Affairs, Genentech, Inc., South San Francisco, California
| | - Nino Kurtsikidze
- Global Product Development and Medical Affairs Oncology, F. Hoffmann-La Roche Ltd., Basel, Switzerland
| | - Katja Schulze
- Translational Medicine, Oncology Biomarker Development, Genentech, Inc., South San Francisco, California
| | - Celina Ngiam
- US Medical Affairs, Genentech, Inc., South San Francisco, California
| | - Jamie E Chaft
- Thoracic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, New York
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11
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Qi Y, Gu L, Shen J, Yao Y, Zhao Y, Lu S, Chen Z. An open, observational clinical study of neoadjuvant therapy in resectable stage III non-small cell lung cancer. Front Oncol 2023; 13:1194100. [PMID: 37655106 PMCID: PMC10467278 DOI: 10.3389/fonc.2023.1194100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 07/26/2023] [Indexed: 09/02/2023] Open
Abstract
Background This open, observational clinical study aimed to investigate the efficacy, safety and survival outcomes of neoadjuvant chemotherapy, neoadjuvant immunotherapy with(out) chemotherapy and neoadjuvant targeted therapy among resectable stage III non-small cell lung cancer (NSCLC) patients (NCT04197076) in real world. 48 of the 57 evaluable patients were included in this interim analysis. Methods This study was conducted at Shanghai Chest Hospital and included eligible NSCLC patients who were 18 years or older and had resectable clinical stage III disease. Surgical resection was conducted after neoadjuvant chemotherapy (13 patients), immunotherapy with(out) chemotherapy (26 patients), and targeted therapy (9 patients). Disease-free survival (DFS) was evaluated as the primary endpoint. The secondary endpoint was pathological complete response (pCR) rate. Clinical response rate (cRR), related adverse events (AEs), surgical feasibility and pathological features were also discussed in this study. Results Significant differences in DFS were noted between chemotherapy and immunotherapy [7.7 months (range, 3.1 to 23.2 months) vs. 9.6 months (range, 4.0 to 47.9 months); P=0.032], and between chemotherapy and targeted therapy [7.7 months (range, 3.1 to 23.2 months) vs. 13.2 months (range, 7.5 to 32.2 months); P=0.015], but not between immunotherapy and targeted therapy (P=0.500). Subgroup analysis also favored neoadjuvant immunotherapy and targeted therapy. 5 patients achieved pathological complete response (pCR), all of whom were in the neoadjuvant immunotherapy arm, leading to a pCR rate of 19.2% in this arm. Treatment-emergent adverse events (TEAEs) of over grade 3 occurred in 11 patients (19.3%), with 5 (29.4%) in the chemotherapy arm, 5 (16.7%) in the immunotherapy arm and 1 (10.0%) in the targeted therapy arm. One grade 4 and one grade 2 surgery-related serious adverse event occurred in the neoadjuvant chemotherapy and immunotherapy arm, respectively. Conclusion In patients diagnosed with resectable stage III NSCLC, neoadjuvant immunotherapy and neoadjuvant targeted therapy were associated with significantly longer disease-free survival compared with neoadjuvant chemotherapy. Clinical and pathological response rates were also higher in the immunotherapy and targeted therapy arm. Adverse events were found to be manageable and similar across all three groups, and surgical feasibility favored immunotherapy or targeted therapy rather than chemotherapy. Clinical trial registration https://clinicaltrials.gov/, identifier NCT04197076.
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Affiliation(s)
| | | | | | | | | | - Shun Lu
- Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhiwei Chen
- Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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12
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Loh J, Low JL, Sachdeva M, Low PQ, Wong RSJ, Huang Y, Chia PL, Soo RA. Management of Oncogene Driven Locally Advanced Unresectable Non-small Cell Lung Cancer. Expert Rev Anticancer Ther 2023; 23:913-926. [PMID: 37551698 DOI: 10.1080/14737140.2023.2245140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 08/02/2023] [Indexed: 08/09/2023]
Abstract
INTRODUCTION The current standard of care of locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemoradiation, followed by consolidation durvalumab. However, there is evidence that the efficacy of chemoradiation and also immunotherapy in many oncogene-positive LA-NSCLC are attenuated, and dependent on the subgroup. AREAS COVERED We will firstly review the outcomes of standard-of-care therapy in oncogene-driven LA-NSCLC. We looked at various oncogene driven subgroups and the tumor microenvironment that may explain differential response. Finally, we review the role of targeted therapy in the treatment of LA-NSCLC. EXPERT OPINION Each oncogene-positive subgroup should be treated as its own entity, and continued efforts should be undertaken to incorporate targeted therapy, which is likely to yield superior survival outcomes if trial design can be optimized and toxicities can be managed.
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Affiliation(s)
- Jerold Loh
- Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, Singapore, Singapore
| | - Jia Li Low
- Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, Singapore, Singapore
| | - Manavi Sachdeva
- Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, Singapore, Singapore
| | - Peter Qj Low
- Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, Singapore, Singapore
| | - Rachel Su Jen Wong
- Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, Singapore, Singapore
| | - Yiqing Huang
- Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, Singapore, Singapore
| | - Puey Ling Chia
- Department of Medical Oncology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Ross A Soo
- Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, Singapore, Singapore
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13
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Lengel HB, Zheng J, Tan KS, Liu CC, Park BJ, Rocco G, Adusumilli PS, Molena D, Yu HA, Riely GJ, Bains MS, Rusch VW, Kris MG, Chaft JE, Li BT, Isbell JM, Jones DR. Clinicopathologic outcomes of preoperative targeted therapy in patients with clinical stage I to III non-small cell lung cancer. J Thorac Cardiovasc Surg 2023; 165:1682-1693.e3. [PMID: 36528430 PMCID: PMC10085825 DOI: 10.1016/j.jtcvs.2022.10.056] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 10/06/2022] [Accepted: 10/29/2022] [Indexed: 11/18/2022]
Abstract
OBJECTIVE Targeted therapy improves outcomes in patients with advanced-stage non-small cell lung cancer (NSCLC) and in the adjuvant setting, but data on its use before surgery are limited. We sought to investigate the safety and feasibility of preoperative targeted therapy in patients with operable NSCLC. METHODS We retrospectively reviewed 51 patients with clinical stage I to III NSCLC who received targeted therapy, alone or in combination with chemotherapy, before surgical resection with curative intent, treated from 2004 to 2021. The primary outcome was the safety and feasibility of preoperative targeted therapy; secondary outcomes included objective response rate, major pathologic response (defined as ≤10% viable tumor) rate, recurrence-free survival (RFS), and overall survival. RESULTS Of the 51 patients included, 46 had an activating epidermal growth factor receptor gene alteration and 5 had an anaplastic lymphoma kinase fusion. Overall, 37 of 46 evaluable patients experienced at least 1 adverse event before surgery; however, only 3 patients experienced a grade 3 or 4 event. The objective response rate was 38% (17/45) for all evaluable patients and 44% (14/32) for patients with clinical stage II or III disease. The major pathologic response rate was 20% (9/44); 2 patients had a complete pathologic response. Median RFS was 3.8 years (95% CI, 2.8 to not reached). Targeted therapy alone was associated with better RFS than combination therapy (P = .009) in patients with clinical stage II or III disease. CONCLUSIONS Preoperative targeted therapy was well tolerated and associated with good outcomes, with or without induction chemotherapy. In addition, radiographic response and pathologic response were strongly correlated.
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Affiliation(s)
- Harry B Lengel
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Junting Zheng
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Kay See Tan
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Corinne C Liu
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Bernard J Park
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Gaetano Rocco
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Prasad S Adusumilli
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Daniela Molena
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Helena A Yu
- Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Gregory J Riely
- Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Manjit S Bains
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Valerie W Rusch
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Mark G Kris
- Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Jamie E Chaft
- Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Bob T Li
- Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - James M Isbell
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
| | - David R Jones
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY.
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14
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Leone GM, Candido S, Lavoro A, Vivarelli S, Gattuso G, Calina D, Libra M, Falzone L. Clinical Relevance of Targeted Therapy and Immune-Checkpoint Inhibition in Lung Cancer. Pharmaceutics 2023; 15:1252. [PMID: 37111737 PMCID: PMC10142433 DOI: 10.3390/pharmaceutics15041252] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 04/12/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
Lung cancer (LC) represents the second most diagnosed tumor and the malignancy with the highest mortality rate. In recent years, tremendous progress has been made in the treatment of this tumor thanks to the discovery, testing, and clinical approval of novel therapeutic approaches. Firstly, targeted therapies aimed at inhibiting specific mutated tyrosine kinases or downstream factors were approved in clinical practice. Secondly, immunotherapy inducing the reactivation of the immune system to efficiently eliminate LC cells has been approved. This review describes in depth both current and ongoing clinical studies, which allowed the approval of targeted therapies and immune-checkpoint inhibitors as standard of care for LC. Moreover, the present advantages and pitfalls of new therapeutic approaches will be discussed. Finally, the acquired importance of human microbiota as a novel source of LC biomarkers, as well as therapeutic targets to improve the efficacy of available therapies, was analyzed. Therapy against LC is increasingly becoming holistic, taking into consideration not only the genetic landscape of the tumor, but also the immune background and other individual variables, such as patient-specific gut microbial composition. On these bases, in the future, the research milestones reached will allow clinicians to treat LC patients with tailored approaches.
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Affiliation(s)
- Gian Marco Leone
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Saverio Candido
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
- Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, 95123 Catania, Italy
| | - Alessandro Lavoro
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Silvia Vivarelli
- Department of Biomedical and Dental Sciences, Morphological and Functional Imaging, Section of Occupational Medicine, University of Messina, 98125 Messina, Italy
| | - Giuseppe Gattuso
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Massimo Libra
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
- Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, 95123 Catania, Italy
| | - Luca Falzone
- Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy;
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15
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Lv C, Fang W, Wu N, Jiao W, Xu S, Ma H, Wang J, Wang R, Ji C, Li S, Wang Y, Yan S, Lu F, Pei Y, Liu Y, Yang Y. Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): A multicenter, single-arm, open-label phase 2b trial. Lung Cancer 2023; 178:151-156. [PMID: 36863124 DOI: 10.1016/j.lungcan.2023.02.011] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 02/11/2023] [Accepted: 02/14/2023] [Indexed: 02/19/2023]
Abstract
OBJECTIVES Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been approved for EGFR-mutant non-small-cell lung cancer (NSCLC). We aimed to evaluate the efficacy and safety of neoadjuvant osimertinib in patients with EGFR-mutant resectable locally advanced NSCLC. MATERIALS AND METHODS This single-arm, phase 2b trial (ChiCTR1800016948) was conducted at six centers in mainland China. Patients with a measurable stage IIA-IIIB (T3-4 N2) lung adenocarcinoma and EGFR exon 19 and/or 21 mutations were enrolled. The patients were treated with osimertinib 80 mg orally once per day for six weeks, followed by surgical resection. The primary endpoint was the objective response rate (ORR) assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. RESULTS Between October 17, 2018, and June 08, 2021, 88 patients were screened for eligibility. Forty patients were enrolled and treated with neoadjuvant osimertinib therapy. The ORR was 71.1 % (27/38) (95 % confidence interval: 55.2-83.0) in 38 patients who completed the 6-week osimertinib treatment. Thirty-two patients underwent surgery, and 30 (93.8 %) underwent successful R0 resection. Thirty (75.0 %) of 40 patients had treatment-related adverse events during neoadjuvant treatment, and three (7.5 %) had treatment-related adverse events of grade 3. The most common treatment-related adverse events were rash (n = 20 [50 %]), diarrhea (n = 12 [30 %]), and oral ulceration (n = 12 [30 %]). CONCLUSIONS The third-generation EGFR TKI osimertinib, with satisfying efficacy and acceptable safety profile, could be a promising neoadjuvant therapy in patients with resectable EGFR-mutant NSCLC.
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Affiliation(s)
- Chao Lv
- Second Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing, China
| | - Wentao Fang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Nan Wu
- Second Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing, China
| | - Wenjie Jiao
- Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shidong Xu
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Haitao Ma
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Jiangsu, China
| | - Jia Wang
- Second Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing, China
| | - Rui Wang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Chunyu Ji
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Shaolei Li
- Second Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing, China
| | - Yuzhao Wang
- Second Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing, China
| | - Shi Yan
- Second Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing, China
| | - Fangliang Lu
- Second Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing, China
| | - Yuquan Pei
- Second Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing, China
| | - Yinan Liu
- Second Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing, China
| | - Yue Yang
- Second Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing, China.
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16
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Tian J, Lin Z, Chen Y, Fu Y, Ding Z. Dramatic response to neoadjuvant savolitinib in marginally resectable lung adenocarcinoma with MET exon 14 skipping mutation: A case report and literature review. Front Oncol 2022; 12:1006634. [PMID: 36387081 PMCID: PMC9646987 DOI: 10.3389/fonc.2022.1006634] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 09/30/2022] [Indexed: 10/15/2023] Open
Abstract
Mesenchymal-epithelial transition (MET) exon 14 skipping mutation (METex14) is a low-frequency driver mutation in metastatic non-small cell lung cancer (NSCLC) (3%-4%) and is associated with a poor prognosis. With the advent of selective MET inhibitors such as capmatinib, tepotinib, and savolitinib, the outcome for these patients was significantly improved. Here, we report a 76-year-old male patient with marginally resectable stage IIIB lung adenocarcinoma harboring METex14 who was successfully treated with savolitinib for neoadjuvant therapy. An 82% shrinkage of the primary tumor was observed, and only 5% of the tumor was viable by pathology in the following radical surgery. A dozen of studies tested the efficiency of neoadjuvant immunotherapy or immunochemotherapy, but for NSCLC with driver mutations, neoadjuvant targeted therapy might be more appropriate. We advocated the neoadjuvant MET TKI treatment for NSCLC.
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Affiliation(s)
| | | | | | | | - Zhenyu Ding
- Department of Biotherapy, Cancer Center, West China Hospital, West China Medical School, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
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17
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Stephan-Falkenau S, Streubel A, Mairinger T, Kollmeier J, Misch D, Thiel S, Bauer T, Pfannschmidt J, Hollmann M, Wessolly M, Blum TG. Landscape of Genomic Alterations and PD-L1 Expression in Early-Stage Non-Small-Cell Lung Cancer (NSCLC)-A Single Center, Retrospective Observational Study. Int J Mol Sci 2022; 23:12511. [PMID: 36293366 PMCID: PMC9604339 DOI: 10.3390/ijms232012511] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 10/13/2022] [Accepted: 10/17/2022] [Indexed: 01/02/2024] Open
Abstract
Precision oncology and immunotherapy have revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). Emerging studies show that targeted therapies are also beneficial for patients with driver alterations such as epidermal growth factor receptor (EGFR) mutations in early-stage NSCLC (stages I-IIIA). Furthermore, patients with elevated programmed death-ligand 1 (PD-L1) expression appear to respond favorably to adjuvant immunotherapy. To determine the frequency of genomic alterations and PD-L1 status in early-stage NSCLC, we retrospectively analyzed data from 2066 unselected, single-center patients with NSCLC diagnosed using next-generation sequencing and immunohistochemistry. Nine-hundred and sixty-two patients (46.9%) presented with early-stage NSCLC. Of these, 37.0% had genomic alterations for which targeted therapies have already been approved for advanced NSCLC. The frequencies of driver mutations in the early stages were equivalent to those in advanced stages, i.e., the rates of EGFR mutations in adenocarcinomas were 12.7% (72/567) and 12.0% (78/650) in early and advanced NSCLC, respectively (p = 0778). In addition, 46.3% of early-stage NSCLC cases were PD-L1-positive, with a tumor proportion score (TPS) of ≥1%. With comparable frequencies of driver mutations in early and advanced NSCLC and PD-L1 overexpression in nearly half of patients with early-stage NSCLC, a broad spectrum of biomarkers for adjuvant and neoadjuvant therapies is available, and several are currently being investigated in clinical trials.
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Affiliation(s)
- Susann Stephan-Falkenau
- Institute for Tissue Diagnostics, MVZ at Helios Klinikum Emil von Behring, 14165 Berlin, Germany
| | - Anna Streubel
- Institute for Tissue Diagnostics, MVZ at Helios Klinikum Emil von Behring, 14165 Berlin, Germany
| | - Thomas Mairinger
- Institute for Tissue Diagnostics, MVZ at Helios Klinikum Emil von Behring, 14165 Berlin, Germany
| | - Jens Kollmeier
- Department of Pneumology, Heckeshorn Lung Clinic, Helios Klinikum Emil von Behring, 14165 Berlin, Germany
| | - Daniel Misch
- Department of Pneumology, Heckeshorn Lung Clinic, Helios Klinikum Emil von Behring, 14165 Berlin, Germany
| | - Sebastian Thiel
- Department of Pneumology, Heckeshorn Lung Clinic, Helios Klinikum Emil von Behring, 14165 Berlin, Germany
| | - Torsten Bauer
- Department of Pneumology, Heckeshorn Lung Clinic, Helios Klinikum Emil von Behring, 14165 Berlin, Germany
| | - Joachim Pfannschmidt
- Department of Thoracic Surgery, Heckeshorn Lung Clinic, Helios Klinikum Emil von Behring, 14165 Berlin, Germany
| | - Manuel Hollmann
- Institute for Tissue Diagnostics, MVZ at Helios Klinikum Emil von Behring, 14165 Berlin, Germany
| | - Michael Wessolly
- Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, 45147 Essen, Germany
| | - Torsten Gerriet Blum
- Department of Pneumology, Heckeshorn Lung Clinic, Helios Klinikum Emil von Behring, 14165 Berlin, Germany
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Liu Y, Zhao C, Lu Q, Hu Y. The optimal neoadjuvant regimen for nonsmall cell lung cancer: A meta-analysis. Medicine (Baltimore) 2022; 101:e30159. [PMID: 36042672 PMCID: PMC9410656 DOI: 10.1097/md.0000000000030159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
OBJECTIVE To compare the efficacy and complications of different neoadjuvant to determine the optimal regimens for nonsmall cell lung cancer (NSCLC) patients. METHODS A systematic search of the Web of Science, and PubMed databases was conducted through June 3, 2021, reporting a comparison of chemotherapy, chemoradiotherapy, and immunotherapy. RESULTS Of 3462 studies, 25 were considered for evidence synthesis. 1035 patients who received chemotherapy or radiotherapy before surgery did not prolong the overall survival (OS) compared with 1038 patients who received surgery alone (hazard ratio [HR] 1.13, 95% CI 1·00-1·28, P = 0·05). 1192 patients received chemoradiotherapy and 864 patients received chemotherapy or radiotherapy; chemoradiotherapy prolonged the OS compared with chemotherapy (HR 0.52, 95% CI 0·29 to 0.95, P = .03). Compared with 110 patients who received other therapy, 93 patients who received immunotherapy had prolonged the OS (HR 1.56, 95% CI 1·08-2·25, P = .02). Chemoradiotherapy increased the pathological response rate (HR 1.68, 95% CI 1·33-2·12, P < .0001), and grade 3 and 4 adverse effects were not increased (HR 5.90, 95% CI 0.88 to 39.60, P = .007). Immunotherapy increased the pathological response (HR 2.79, 95% CI 1·71-4·54, P < .0001), with no significant effects on grades 3 and 4 adverse(HR 0.71, 95% CI 0·19-2·64, P = .61). CONCLUSION Our data showed that chemotherapy may prolong OS and PFS, but not statistically significant; however, the combination of chemotherapy and radiation did show an advantage, and immunotherapy may be also the choice for neoadjuvant therapy.
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Affiliation(s)
- Yi Liu
- Department of Thoracic Surgery, The People’s Hospital of Yichun City, Jiangxi, 336028, China
| | - Chong Zhao
- Department of Respiratory, The People’s Hospital of Yichun City, Jiangxi, 336028, China
| | - Qiuliang Lu
- Department of Thoracic Surgery, The People’s Hospital of Yichun City, Jiangxi, 336028, China
| | - Yirong Hu
- Department of Neurology, The People’s Hospital of Yichun City, Jiangxi, 336028, China
- *Correspondence: Yirong Hu, No 88, Zhongshan Western Road, Yichun, Jiangxi 336028, China (e-mail: )
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Pecci F, Cantini L, Metro G, Ricciuti B, Lamberti G, Farooqi AA, Berardi R. Non-small-cell lung cancer: how to manage EGFR-mutated disease. Drugs Context 2022; 11:2022-4-1. [PMID: 35975029 PMCID: PMC9354708 DOI: 10.7573/dic.2022-4-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 06/10/2022] [Indexed: 11/23/2022] Open
Abstract
The treatment of non-small-cell lung cancer (NSCLC) harbouring EGFR mutations has witnessed some major breakthroughs in the last years. On the one hand, the recent advent of the third-generation tyrosine kinase inhibitor (TKI) osimertinib has reshaped the therapeutic algorithm both in the first-line and adjuvant settings for patients with common activating Ex19del and L858R EGFR mutations. On the other hand, the availability of new comprehensive next-generation sequencing panels, to be used on tumour tissue or on liquid biopsy, has revealed the existence of uncommon as well as compound mutations that partially explain the onset of resistance. Nevertheless, dissecting the biological mechanisms underlying primary and secondary resistance to EGFR-TKIs is crucial to developing alternative therapeutic strategies and further improving patient outcomes. Herein, we provide an updated and comprehensive summary of the latest advancements in the quest for compounds targeting EGFR-mutant advanced non-small-cell lung cancer, discussing the biological rationale underlying the development of a forefront combination of TKI and/or new antibody-drug conjugates. We also suggest a treatment algorithm that could be followed considering the latest published data.
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Affiliation(s)
- Federica Pecci
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti di Ancona, Ancona, Italy
| | - Luca Cantini
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti di Ancona, Ancona, Italy
| | - Giulio Metro
- Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy
| | - Biagio Ricciuti
- Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
- Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Giuseppe Lamberti
- Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Bologna, Italy
| | | | - Rossana Berardi
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti di Ancona, Ancona, Italy
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20
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Muthusamy B, Patil PD, Pennell NA. Perioperative Systemic Therapy for Resectable Non-Small Cell Lung Cancer. J Natl Compr Canc Netw 2022; 20:953-961. [PMID: 35948038 DOI: 10.6004/jnccn.2022.7021] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 04/26/2022] [Indexed: 12/25/2022]
Abstract
Despite remarkable treatment advancements in patients with advanced non-small cell lung cancer (NSCLC), recurrence rates for those with resectable, early-stage disease remains high. Immune checkpoint inhibitors and targeted therapies are 2 promising treatment modalities that may improve survival outcomes for patients with resected NSCLC when moved from the advanced stage to the curable setting. There are many clinical studies that have evaluated or are currently evaluating immunotherapy or targeted therapy in the perioperative setting, and recent trials such as CheckMate 816, ADAURA, and IMpower010 have led to new approvals and demonstrated the promise of this approach. This review discusses recent and ongoing neoadjuvant and adjuvant systemic therapy trials in NSCLC, and where the field may be going in the near future.
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21
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Hou X, Shi X, Luo J. Efficacy and safety of camrelizumab (a PD‑1 inhibitor) combined with chemotherapy as a neoadjuvant regimen in patients with locally advanced non‑small cell lung cancer. Oncol Lett 2022; 24:215. [PMID: 35720491 PMCID: PMC9178701 DOI: 10.3892/ol.2022.13336] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 04/28/2022] [Indexed: 11/17/2022] Open
Abstract
Camrelizumab is a novel programmed cell death protein 1 (PD-1) inhibitor developed in China that exhibits good efficacy in several advanced cancer types, including non-small cell lung cancer (NSCLC); however, its utility as a neoadjuvant regimen in NSCLC remains unclear. Thus, the present study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy in patients with locally advanced NSCLC. A total of 56 patients with stage IIIA/IIIB resectable NSCLC were analyzed in the present prospective observational study. Amongst the cohort, 31 patients underwent neoadjuvant camrelizumab (200 mg every 2 weeks) plus paclitaxel and carboplatin (PC) chemotherapy, while another 25 cases underwent neoadjuvant PC chemotherapy alone. The pathological response, disease-free survival (DFS) time, overall survival (OS) time and adverse events (AEs) were analyzed. The complete pathological response (25.8 vs. 8.3%; P=0.159) and major pathological response (MPR) (61.3 vs. 37.5%; P=0.080) rates were higher in the camrelizumab plus PC group compared with the findings in the PC group, although the results were not statistically significant. DFS time was significantly prolonged in the camrelizumab plus PC group compared with that in the PC group (P=0.030); however, there was no difference in OS time between these two groups (P=0.251). Following adjustment by multivariate analysis, the camrelizumab plus PC regimen versus the PC regimen alone was independently associated with higher MPR [odds ratio, 5.216; 95% confidence interval (CI), 1.178-23.086; P=0.030], and favorable DFS [hazard ratio (HR), 0.055; 95% CI, 0.007-0.442; P=0.006] and OS (HR, 0.025; 95% CI, 0.002-0.416; P=0.010) times. The most common AEs of the neoadjuvant camrelizumab plus PC regimen were alopecia (51.6%), nausea and vomiting (45.2%), anemia (41.9%) and fatigue (41.9%), the majority of which occurred in patients with grade 1–2 disease. The present results indicated that neoadjuvant camrelizumab plus PC chemotherapy exhibited a superior pathological response and survival profile to PC chemotherapy alone, and was well tolerated in patients with locally advanced NSCLC.
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Affiliation(s)
- Xinlei Hou
- Department of Thoracic Surgery, Daqing Oil Field General Hospital, Daqing, Heilongjiang 163001, P.R. China
| | - Xueliang Shi
- Department of Thoracic Surgery, Daqing Oil Field General Hospital, Daqing, Heilongjiang 163001, P.R. China
| | - Jie Luo
- Department of Ophthalmology, Daqing Oil Field General Hospital, Daqing, Heilongjiang 163001, P.R. China
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22
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Cansouline X, Lipan B, Sizaret D, Tallet A, Vandier C, Carmier D, Legras A. EGFR-Mutant Non-Small-Cell Lung Cancer at Surgical Stages: What Is the Place for Tyrosine Kinase Inhibitors? Cancers (Basel) 2022; 14:cancers14092257. [PMID: 35565386 PMCID: PMC9099844 DOI: 10.3390/cancers14092257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 04/23/2022] [Accepted: 04/27/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary Tyrosine kinase inhibitors are drugs targeting the epidermal growth factor receptor. In lung cancer, they are used to treat advanced EGFR-mutant diseases, and more recently, one has been approved for adjuvant therapy. Even though publications on the topic are numerous, conclusions are difficult to interpret and are sometimes contradictory. We therefore reviewed the literature in order to present an overview of up-to-date data regarding the adjuvant and neoadjuvant use of tyrosine kinase inhibitors, with particular attention given to their benefits, proven or expected, as well as what challenges could be faced when entering them as protocols in standard care. Abstract The ADAURA trial has been significant for the perception of EGFR tyrosine kinase inhibitors (TKIs) as a tool for early stage non-small-cell lung cancer (NSCLC). It produced such great insight that the main TKI, Osimertinib, was rapidly integrated into international guidelines for adjuvant use. However, EGFR-mutant NSCLC is a complex entity and has various targeting drugs, and the benefits for patients might not be as clear as they seem. We reviewed trials and meta-analyses considering TKI adjuvant and neoadjuvant use. We also explored the influence of mutation variability and financial evaluations. We found that TKIs often show disease-free survival (DFS) benefits, yet studies have struggled to improve the overall survival (OS); however, the results from the literature might be confusing because of variability in the stages and mutations. The safety profiles and adverse events are acceptable, but costs remain high and accessibility might not be optimal. TKIs are promising drugs that could allow for tailored treatment designs.
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Affiliation(s)
- Xavier Cansouline
- Department of Thoracic Surgery, Tours University Hospital, 37170 Chambray-Lès-Tours, France; (X.C.); (B.L.)
- Nutrition, Croissance et Cancer, INSERM UMR 1069, University of Tours, 37000 Tours, France;
| | - Béatrice Lipan
- Department of Thoracic Surgery, Tours University Hospital, 37170 Chambray-Lès-Tours, France; (X.C.); (B.L.)
| | - Damien Sizaret
- Department of Pathology, Tours University Hospital, 37170 Chambray-Lès-Tours, France;
| | - Anne Tallet
- Platform of Solid Tumor Molecular Genetics, Tours University, 37000 Tours, France;
| | - Christophe Vandier
- Nutrition, Croissance et Cancer, INSERM UMR 1069, University of Tours, 37000 Tours, France;
| | - Delphine Carmier
- Department of Pneumology, Tours University Hospital, 37000 Tours, France;
| | - Antoine Legras
- Department of Thoracic Surgery, Tours University Hospital, 37170 Chambray-Lès-Tours, France; (X.C.); (B.L.)
- Nutrition, Croissance et Cancer, INSERM UMR 1069, University of Tours, 37000 Tours, France;
- Correspondence: ; Tel.: +33-2474-746-36
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23
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Deng HY, Li D, Ren Y, Wang K, Tang X. Targeted Therapy Followed by Salvage Surgery and Adjuvant Therapy: A Promising Therapy for Lung Cancer With Malignant Pleural Effusion From a Case Report. Front Surg 2021; 8:659983. [PMID: 34957195 PMCID: PMC8702428 DOI: 10.3389/fsurg.2021.659983] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 11/10/2021] [Indexed: 02/05/2023] Open
Abstract
Introduction: Malignant pleural effusion was encountered in about 8–15% of lung cancer patients at initial cancer diagnosis. The optimal therapeutic strategies for lung cancer with malignant pleural effusion (MPE) remain unclear. Case Description: In this study, we reported a case of lung cancer with MPE, which was successfully managed with a multidisciplinary therapeutic strategy. The patient initially received gefitinib for 4 months with excellent response and he underwent salvage thoracoscopic lobectomy and systematic lymphadenectomy. Pathological complete response was confirmed for the patient and he discontinued gefitinib but received 4 cycles of adjuvant chemotherapy instead. The patient is still alive without disease progression for 62 months after surgery. Conclusions: Combining targeted therapy, salvage surgery, and adjuvant therapy may be a promising treatment strategy for lung cancer with MPE harboring oncogene-targeted mutations.
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Affiliation(s)
- Han-Yu Deng
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Deyan Li
- Operating Room, West China Hospital, Sichuan University, Chengdu, China
| | - Ying Ren
- Department of Outpatient, West China Hospital, Sichuan University, Chengdu, China
| | - Ke Wang
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaojun Tang
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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24
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Sotelo MJ, Luis García J, Torres-Mattos C, Milián H, Carracedo C, González-Ruiz MÁ, Mielgo-Rubio X, Trujillo-Reyes JC, Couñago F. Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer. World J Clin Oncol 2021; 12:912-925. [PMID: 34733613 PMCID: PMC8546659 DOI: 10.5306/wjco.v12.i10.912] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 07/29/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Patients with early-stage non-small-cell lung cancer (NSCLC) are candidates for curative surgery; however, despite multiple advances in lung cancer management, recurrence rates remain high. Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival (OS), but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients. The high efficacy of tyrosine kinase inhibitors (TKIs) against epidermal growth factor receptor-mutated (EGFR) in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease. Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment, in patients with resected EGFR-mutated NSCLC, and shown that they significantly prolong disease-free survival (DFS), but this benefit does not translate to OS. Recently, an interim analysis of the ADAURA trial demonstrated that, surprisingly, osimertinib improved DFS. This led to the study being stopped early, leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup. These targeted agents are also being evaluated in locally-advanced disease, with promising results, although prospective studies with larger sample sizes are needed to confirm these results. In this article, we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.
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Affiliation(s)
- Miguel J Sotelo
- Department of Medical Oncology, Hospital María Auxiliadora; Department of Medical Oncology, Centro Oncológico Aliada; Oncological Research Unit, Clínica San Gabriel, Lima 15801, Peru
| | - José Luis García
- Department of Thoracic Surgery, Hospital Universitario La Princesa; Department of Thoracic Surgery, MD Anderson Cancer Center; Department of Thoracic Surgery, Hospital HM, Madrid 28006, Spain
| | - Cesar Torres-Mattos
- Department of Medical Oncology, Hospital Nacional Guillermo Almenara; Oncological Research Unit, Clínica San Gabriel, Lima 15033, Peru
| | - Héctor Milián
- Department of Thoracic Surgery, Hospital Universitario La Princesa, Madrid 28006, Spain
| | - Carlos Carracedo
- Department of Medical Oncology, Centro Oncológico Aliada, Lima 15036, Peru
| | | | - Xabier Mielgo-Rubio
- Department of Oncology, Hospital Universitario Fundación Alcorcón, Alcorcón 28922, Madrid, Spain
| | | | - Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid; Hospital La Luz; Universidad Europea de Madrid, Madrid 28223, Spain
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25
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Belluomini L, Riva ST, Simbolo M, Nocini R, Trestini I, Avancini A, Tregnago D, Ferrara MG, Caldart A, Dodi A, Caliò A, Bria E, Scarpa A, Milella M, Menis J, Pilotto S. Anticipating EGFR Targeting in Early Stages of Lung Cancer: Leave No Stone Unturned. Cells 2021; 10:2685. [PMID: 34685665 PMCID: PMC8535007 DOI: 10.3390/cells10102685] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/05/2021] [Accepted: 10/06/2021] [Indexed: 12/20/2022] Open
Abstract
Background: The current treatment landscape of early stage lung cancer is rapidly evolving, particularly in EGFR mutant non-small cell lung cancer (NSCLC), where target therapy is moving to early stages. In the current review, we collected the available data exploring the impact of EGFR targeting in both neoadjuvant and adjuvant settings, underlying lights and shadows and discussing the existing open issues. Methods: We performed a comprehensive search using PubMed and the proceedings of major international meetings to identify neoadjuvant/adjuvant trials with EGFR tyrosine kinase inhibitors (TKIs) in NSCLC. Results: Limited data are available so far about the activity/efficacy of neoadjuvant TKIs in EGFR mutant NSCLC, with only modest downstaging and pathological complete response rates reported. Differently, the ADAURA trial already proposed osimertinib as a potential new standard of care in resected NSCLC harboring an activating EGFR mutation. Conclusion: Anticipating targeted therapy to early stage EGFR mutant NSCLC presents great opportunities but also meaningful challenges in the current therapeutic/diagnostic pathway of lung cancer care. Appropriate endpoint(s) selection for clinical trials, disease progression management, patients' and treatment selection, as well as need to address the feasibility of molecular profiling anticipation, represent crucial issues to face before innovation can move to early stages.
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Affiliation(s)
- Lorenzo Belluomini
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, 37134 Verona, Italy; (L.B.); (S.T.R.); (I.T.); (A.A.); (D.T.); (A.C.); (A.D.); (M.M.); (J.M.)
| | - Silvia Teresa Riva
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, 37134 Verona, Italy; (L.B.); (S.T.R.); (I.T.); (A.A.); (D.T.); (A.C.); (A.D.); (M.M.); (J.M.)
| | - Michele Simbolo
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy; (M.S.); (A.C.); (A.S.)
| | - Riccardo Nocini
- Otolaryngology—Head and Neck Surgery Department, University of Verona Hospital Trust, 37126 Verona, Italy;
| | - Ilaria Trestini
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, 37134 Verona, Italy; (L.B.); (S.T.R.); (I.T.); (A.A.); (D.T.); (A.C.); (A.D.); (M.M.); (J.M.)
| | - Alice Avancini
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, 37134 Verona, Italy; (L.B.); (S.T.R.); (I.T.); (A.A.); (D.T.); (A.C.); (A.D.); (M.M.); (J.M.)
| | - Daniela Tregnago
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, 37134 Verona, Italy; (L.B.); (S.T.R.); (I.T.); (A.A.); (D.T.); (A.C.); (A.D.); (M.M.); (J.M.)
| | - Miriam Grazia Ferrara
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00100 Rome, Italy; (M.G.F.); (E.B.)
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00100 Rome, Italy
| | - Alberto Caldart
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, 37134 Verona, Italy; (L.B.); (S.T.R.); (I.T.); (A.A.); (D.T.); (A.C.); (A.D.); (M.M.); (J.M.)
| | - Alessandra Dodi
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, 37134 Verona, Italy; (L.B.); (S.T.R.); (I.T.); (A.A.); (D.T.); (A.C.); (A.D.); (M.M.); (J.M.)
| | - Anna Caliò
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy; (M.S.); (A.C.); (A.S.)
| | - Emilio Bria
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00100 Rome, Italy; (M.G.F.); (E.B.)
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00100 Rome, Italy
| | - Aldo Scarpa
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy; (M.S.); (A.C.); (A.S.)
| | - Michele Milella
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, 37134 Verona, Italy; (L.B.); (S.T.R.); (I.T.); (A.A.); (D.T.); (A.C.); (A.D.); (M.M.); (J.M.)
| | - Jessica Menis
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, 37134 Verona, Italy; (L.B.); (S.T.R.); (I.T.); (A.A.); (D.T.); (A.C.); (A.D.); (M.M.); (J.M.)
| | - Sara Pilotto
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, 37134 Verona, Italy; (L.B.); (S.T.R.); (I.T.); (A.A.); (D.T.); (A.C.); (A.D.); (M.M.); (J.M.)
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Chen D, Jin Z, Zhang J, Xu C, Zhu K, Ruan Y, Zhang B, Chen B, Shen J. Efficacy and Safety of Neoadjuvant Targeted Therapy vs. Neoadjuvant Chemotherapy for Stage IIIA EGFR-Mutant Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Front Surg 2021; 8:715318. [PMID: 34490338 PMCID: PMC8417411 DOI: 10.3389/fsurg.2021.715318] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 07/26/2021] [Indexed: 12/25/2022] Open
Abstract
Purpose: The role of targeted therapy in the neoadjuvant field of stage IIIA epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is still controversial. We sought to evaluate the efficacy and safety of neoadjuvant targeted therapy (NTT) with neoadjuvant chemotherapy (NCT) used as a benchmark comparator. Methods: A systematic search was conducted in four databases (Pubmed, Cochrane Library, Embase, CNKI) for eligible studies on NTT published before October 2020. The primary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade 3/4 adverse events (AEs). Statistical analysis and bias assessment were performed by RevMan 5.3. Results: A total of 319 patients, including 3 randomized controlled trials and 2 non-randomized controlled trials, were included in the meta-analysis. Perform the second subgroup analysis after excluding 2 non-randomized controlled trials. The meta-analysis reveals that, for EGFR mutation-positive stage IIIA NSCLC patients, compared with NCT, NTT can significantly increase ORR (relative risk [RR]:1.70, 95% confidence interval [CI]:1.35–2.15; subgroup-RR:1.56, 95% CI 1.23–2.0) and significantly reduce grade 3/4 AEs (RR:0.5, 95% CI 0.34–0.75; subgroup-RR: 0.53, 95% CI 0.26–1.08). The OS of the NTT arm is slightly higher, but the difference is not significant (hazards ratio [HR]: 0.74, 95% CI: 0.43–1.27; subgroup-HR: 0.64 95% CI 0.40–1.03). No difference in PFS was found (HR: 0.81, 95% CI 0.27–2.44). Conclusion: In neoadjuvant setting, targeted therapy has a definitive effect on patients with EGFR mutation-positive stage IIIA NSCLC and is even better than chemotherapy in terms of toxicity and tumor response rate. Systematic Review Registration: PROSPERO, identifier CRD42021221136.
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Affiliation(s)
- Dong Chen
- Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Zixian Jin
- Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Jian Zhang
- Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Congcong Xu
- Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Kanghao Zhu
- Department of Thoracic Surgery, Taizhou Hospital, Zhejiang University, Linhai, China
| | - Yuhang Ruan
- Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Bo Zhang
- Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Baofu Chen
- Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Jianfei Shen
- Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
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Tsuboi M, Weder W, Escriu C, Blakely C, He J, Dacic S, Yatabe Y, Zeng L, Walding A, Chaft JE. Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA. Future Oncol 2021; 17:4045-4055. [PMID: 34278827 PMCID: PMC8530153 DOI: 10.2217/fon-2021-0549] [Citation(s) in RCA: 121] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Osimertinib is a third-generation, irreversible oral EGFR-tyrosine kinase inhibitor), that potently inhibits EGFR-tyrosine kinase inhibitor-sensitizing mutations and T790M resistance mutations together with efficacy in CNS metastases in patients with non-small-cell lung cancer (NSCLC). Here we describe the rationale and design for the Phase III NeoADAURA study (NCT04351555), which will evaluate neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone prior to surgery, in patients with resectable stage II-IIIB N2 EGFR mutation-positive NSCLC. The primary end point is centrally assessed major pathological response at the time of resection. Secondary end points include event-free survival, pathological complete response, nodal downstaging at the time of surgery, disease-free survival, overall survival and health-related quality of life. Safety and tolerability will also be assessed. Trial Registration number: NCT04351555 (ClinicalTrials.gov).
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Affiliation(s)
- Masahiro Tsuboi
- National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan
| | - Walter Weder
- Thoraxchirurgie Klinik Bethanien, Zürich, 8044, Switzerland
| | - Carles Escriu
- The Clatterbridge Cancer Centre, Bebington, Wirral, CH63 4JY, UK
| | - Collin Blakely
- Department of Medicine, University of California, San Francisco, CA 94158-2140, USA
| | - Jianxing He
- The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Sanja Dacic
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
| | | | | | | | - Jamie E Chaft
- Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center & Weill Cornell Medical College, New York, NY 10021, USA
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Shi X, Dong X, Zhai J, Liu X, Lu D, Ni Z, Wu H, Cai K. Current Evidence of the Efficacy and Safety of Neoadjuvant EGFR-TKIs for Patients With Non-small Cell Lung Cancer. Front Oncol 2021; 11:608608. [PMID: 34109108 PMCID: PMC8181135 DOI: 10.3389/fonc.2021.608608] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 04/30/2021] [Indexed: 12/17/2022] Open
Abstract
Purpose Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been indicated to be an effective treatment for advanced EGFR-mutant NSCLC. However, the neoadjuvant application of EGFR-TKIs in resectable NSCLC needs further investigation. Here, we aimed to evaluate the efficacy and safety of neoadjuvant EGFR-TKIs for lung cancer. Methods Published studies on neoadjuvant EGFR-TKIs in NSCLC were identified in PubMed, Web of Science, and EMBASE until June 1, 2020. Data on surgical rates, objective response rates (ORRs), pathologic responses, and adverse event (AE) rates were retrieved for proportional meta-analysis. Results In total, 7 enrolled studies involving 129 EGFR-TKI-sensitive NSCLC patients were included in this analysis. The overall surgical rate in these studies was 95% (95% CI: 83% to 100%), with an ORR of 48% (95% CI: 39% to 57%) in the population with EGFR-TKI-sensitive mutations, whereas the ORR including wild-type EGFR patients was 28% (95% CI: 14% to 44%). The rate of grade 1-2 AEs was 69% (95% CI: 41% to 91%) but with an acceptable rate of grade 3-4 AEs of 0% (95% CI: 0% to 5%). The pooled rates of rash and diarrhea were 56% (95% CI: 31% to 79%) and 25% (95% CI: 6% to 51%), respectively. The impact of neoadjuvant EGFR-TKIs on survival remains inconclusive. Conclusions Neoadjuvant EGFR-TKIs showed objective responses in approximately half of EGFR-sensitive NSCLC patients with a tolerable adverse effect profile. The favorable impact of neoadjuvant EGFR-TKIs on NSCLC needs more evidence for validation, such as the comparison of survival improvement between EGFR-TKIs and chemotherapy. The efficacy of neoadjuvant next-generation EGFR-TKIs in clinical trials remains unclear.
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Affiliation(s)
- Xiaoshun Shi
- Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaoying Dong
- Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jianxue Zhai
- Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiguang Liu
- Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Di Lu
- Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhen Ni
- Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hua Wu
- Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Kaican Cai
- Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
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29
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Montemuiño Muñiz S, Marcos Sánchez S, Calzas Rodríguez J, Losada Vila B, Llorente Herrero E, Hisado Díaz MD, Valeri-Busto González V, Taboada Valladares B, Vaquero Barrón B, Marcos Jimenez FJ, Amor Alonso S, Moradiellos J, Rodríguez de Dios N, Couñago F. Advances in multimodal treatment for stage IIIA-N2 non-small cell lung cancer. J Clin Transl Res 2021; 7:185-198. [PMID: 34104821 PMCID: PMC8177852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 12/09/2020] [Accepted: 03/18/2021] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND AND AIM In Stage IIIA-N2 non-small cell lung cancer (NSCLC), the accuracy of combined positron-emission tomography/computed tomography imaging (PET-CT), together with mediastinal staging techniques, has led to a wide range of challenging clinical scenarios in terms of therapeutic management. Concurrent chemoradiotherapy followed by consolidation immunotherapy remains the standard of care. In patients with potentially-resectable disease, surgery plays an important role in multimodal therapy. The introduction of targeted therapies and immune-checkpoint inhibitors has revolutionized multimodal treatment. In the present article, we review current treatment options and future trends in stage IIIA-N2 NSCLC. RELEVANCE FOR PATIENTS This article provides insight into the current status of multimodal treatment for NSCLC to support decision-making in routine clinical practice.
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Affiliation(s)
- Sara Montemuiño Muñiz
- Department of Radiation Oncology, Hospital Universitario de
Fuenlabrada, Camino del Molino, 2, 28942, Fuenlabrada, Madrid, Sara
Montemuiño, Spain
| | - Soraya Marcos Sánchez
- Department of Radiation Oncology, Hospital Universitario de
Fuenlabrada, Camino del Molino, 2, 28942, Fuenlabrada, Madrid, Sara
Montemuiño, Spain
| | - Julia Calzas Rodríguez
- Department of Medical Oncology, Hospital Universitario de
Fuenlabrada, Camino del Molino, 2, 28942, Fuenlabrada, Madrid, Spain
| | - Beatriz Losada Vila
- Department of Medical Oncology, Hospital Universitario de
Fuenlabrada, Camino del Molino, 2, 28942, Fuenlabrada, Madrid, Spain
| | - Esther Llorente Herrero
- Department of Nuclear Medicine, Hospital Universitario de
Fuenlabrada, Camino del Molino, 2, 28942, Fuenlabrada, Madrid, Spain
| | - María Dolores Hisado Díaz
- Department of Pulmonology, Hospital Universitario de
Fuenlabrada, Camino del Molino, 2, 28942, Fuenlabrada, Madrid, Spain
| | - Victoria Valeri-Busto González
- Department of Pulmonology, Hospital Universitario de
Fuenlabrada, Camino del Molino, 2, 28942, Fuenlabrada, Madrid, Spain
| | - Begoña Taboada Valladares
- Department of Radiation Oncology, Complexo Hospitalario
Universitario Santiago de Compostela, Choupana s/n, bloque d, Santiago de
Compostela, A Coruña, Spain
| | - Blanca Vaquero Barrón
- Department of Radiation Oncology, Hospital Universitario de
La Princesa, C/Diego de León, 62, 28006, Madrid, Spain
| | - Francisco José Marcos Jimenez
- Department of Radiation Oncology, Hospital Universitario de
Cáceres, Avda, Universidad 75, 10004, Cáceres, Extremadura,
Spain
| | - Sergio Amor Alonso
- Department of Thoracic Surgery, Hospital Universitario
Quirónsalud Madrid, C/Diego de Velázquez, 1, 28223, Pozuelo de
Alarcón, Madrid, Spain
| | - Javier Moradiellos
- Department of Thoracic Surgery, Hospital Universitario
Quirónsalud Madrid, C/Diego de Velázquez, 1, 28223, Pozuelo de
Alarcón, Madrid, Spain
| | - Núria Rodríguez de Dios
- Department of Radiation Oncology, Hospital del Mar, Passeig
Marítim, 25-29, 08003 Barcelona, Spain
- IMIM (Hospital del Mar Medical Research Institute),
Barcelona, Spain
- Pompeu Fabra University, Barcelona, Doctor Aiguader, 80,
08003 Barcelona
| | - Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario
Quirónsalud Madrid, C/Diego de Velázquez, 1, 28223, Pozuelo de
Alarcón, Madrid, Spain
- Hospital La Luz, Calle del Maestro Ángel Llorca 8,
28003, Madrid, Spain
- Universidad Europea de Madrid, Calle Tajo, s/n, 28670
Villaviciosa de Odón, Madrid, Spain
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30
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Targeted Therapies in Early Stage NSCLC: Hype or Hope? Int J Mol Sci 2020; 21:ijms21176329. [PMID: 32878298 PMCID: PMC7504271 DOI: 10.3390/ijms21176329] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 08/24/2020] [Accepted: 08/26/2020] [Indexed: 12/25/2022] Open
Abstract
Non-small-cell lung cancer (NSCLC) represents roughly 85% of lung cancers, with an incidence that increases yearly across the world. The introduction in clinical practice of several new and more effective molecules has led to a consistent improvement in survival and quality of life in locally advanced and metastatic NSCLC. In particular, oncogenic drivers have indeed transformed the therapeutic algorithm for NSCLC. Nearly 25% of patients are diagnosed in an early stage when NSCLC is still amenable to radical surgery. In spite of this, five-year survival rates for fully resected early stage remains rather disappointing. Adjuvant chemotherapy has shown a modest survival benefit depending on the stage, but more than half of patients relapse. Given this need for improvement, over the last years different targeted therapies have been evaluated in early-stage NSCLC with no survival benefit in unselected patients. However, the identification of reliable predictive biomarkers to these agents in the metastatic setting, the design of molecularly-oriented studies, and the availability of novel potent and less toxic agents opened the way for a novel era in early stage NSCLC treatment. In this review, we will discuss the current landscape of targeted therapeutic options in early NSCLC.
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