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Sugitani I, Kiyota N, Ito Y, Onoda N, Hiromasa T, Horiuchi K, Kinuya S, Kondo T, Moritani S, Sugino K, Hara H. The 2024 revised clinical guidelines on the management of thyroid tumors by the Japan Association of Endocrine Surgery. Endocr J 2025; 72:545-635. [PMID: 40058844 PMCID: PMC12086281 DOI: 10.1507/endocrj.ej24-0644] [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] [Received: 11/27/2024] [Accepted: 12/31/2024] [Indexed: 05/09/2025] Open
Abstract
The Japan Association of Endocrine Surgery published the first edition of the "Clinical guidelines on the management of thyroid tumors" in 2010 and the revised edition in 2018. The guideline presented herein is the English translation of the revised third edition, issued in 2024. The aim is to enhance health outcomes for patients suffering from thyroid tumors by facilitating evidence-based shared decision-making between healthcare providers and patients, as well as standardizing the management of thyroid tumors. The focus is on adult patients with thyroid tumors, addressing clinically significant issues categorized into areas such as an overview of the diagnosis and treatment of thyroid nodules, treatment strategies by histological type, radioactive iodine therapy, treatment of advanced differentiated carcinoma, pharmacotherapy, and complications and safety management associated with thyroid surgery. Thirty-two clinical questions were established in these areas. Following a comprehensive search of the literature and systematic review to evaluate the overall evidence, we aimed to present optimal recommendations by considering the balance of benefits and harms from the patient's perspective. We integrated evidence and clinical experience to determine the "Certainty of evidence" and "Strength of recommendations". Based on these, we illustrated overall flows of care as "Clinical algorithms". Necessary background knowledge of diseases and established clinical procedures for understanding the recommendations are presented in "Notes", while information that may be clinically useful but for which evidence remains insufficient is included in "Columns", based on the current state of evidence. Finally, future challenges for the next revision are presented as "Future research questions".
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Affiliation(s)
- Iwao Sugitani
- Department of Endocrine Surgery, Nippon Medical School, Tokyo 113-8603, Japan
- the Task Force of the Japan Association of Endocrine Surgery on the Guidelines for Thyroid Tumors
| | - Naomi Kiyota
- Department of Medical Oncology and Hematology, Cancer Center, Kobe University Hospital, Kobe 650-0017, Japan
- the Task Force of the Japan Association of Endocrine Surgery on the Guidelines for Thyroid Tumors
| | - Yasuhiro Ito
- Department of Surgery, Kuma Hospital, Kobe 650-0011, Japan
- the Task Force of the Japan Association of Endocrine Surgery on the Guidelines for Thyroid Tumors
| | - Naoyoshi Onoda
- Department of Surgery, Kuma Hospital, Kobe 650-0011, Japan
- the Task Force of the Japan Association of Endocrine Surgery on the Guidelines for Thyroid Tumors
| | - Tomo Hiromasa
- Department of Nuclear Medicine, Kanazawa University Hospital, Kanazawa 920-8641, Japan
- the Task Force of the Japan Association of Endocrine Surgery on the Guidelines for Thyroid Tumors
| | - Kiyomi Horiuchi
- Department of Endocrine Surgery, Tokyo Women’s Medical University, Tokyo 162-8666, Japan
- the Task Force of the Japan Association of Endocrine Surgery on the Guidelines for Thyroid Tumors
| | - Seigo Kinuya
- Department of Nuclear Medicine, Kanazawa University, Kanazawa 920-8641, Japan
- the Task Force of the Japan Association of Endocrine Surgery on the Guidelines for Thyroid Tumors
| | - Tetsuo Kondo
- Department of Pathology, University of Yamanashi, Yamanashi 409-3898, Japan
- the Task Force of the Japan Association of Endocrine Surgery on the Guidelines for Thyroid Tumors
| | - Sueyoshi Moritani
- Center for Head and Neck Thyroid Surgery, Oumi Medical Center, Shiga 525-8585, Japan
- the Task Force of the Japan Association of Endocrine Surgery on the Guidelines for Thyroid Tumors
| | - Kiminori Sugino
- Surgical Branch, Ito Hospital, Tokyo 150-8308, Japan
- the Task Force of the Japan Association of Endocrine Surgery on the Guidelines for Thyroid Tumors
| | - Hisato Hara
- Department of Breast and Endocrine Surgery, University of Tsukuba, Tsukuba 305-8576, Japan
- the Task Force of the Japan Association of Endocrine Surgery on the Guidelines for Thyroid Tumors
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French JD, Haugen BR, Worden FP, Bowles DW, Gianoukakis AG, Konda B, Dadu R, Sherman EJ, McCue S, Foster NR, Nikiforov YE, Farias TD, Norman PJ, Wirth LJ. Combination Targeted Therapy with Pembrolizumab and Lenvatinib in Progressive, Radioiodine-Refractory Differentiated Thyroid Cancers. Clin Cancer Res 2024; 30:3757-3767. [PMID: 38922338 PMCID: PMC11883846 DOI: 10.1158/1078-0432.ccr-23-3417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 04/08/2024] [Accepted: 06/21/2024] [Indexed: 06/27/2024]
Abstract
PURPOSE Lenvatinib, a potent multikinase inhibitor, improves progression-free survival (PFS) in patients with radioiodine (RAI)-refractory differentiated thyroid cancer; however, most patients experience disease progression, warranting further therapy. We evaluated the efficacy and safety of lenvatinib plus pembrolizumab in these patients. PATIENTS AND METHODS We enrolled patients with progressive, RAI-refractory differentiated thyroid cancer who were either naïve to multikinase inhibitors (cohort 1) or who had progressed on lenvatinib (cohort 2). Patients received oral lenvatinib daily (cohort 1, 20 mg; cohort 2, dose at progression) and intravenous pembrolizumab (200 mg) every 21 days. RESULTS In cohorts 1 and 2, 30 and 27 patients were enrolled, respectively. Adverse events were consistent with those observed in other cancers. In cohort 1, the confirmed overall response rate was 65.5%. There were no complete responses (primary endpoint). The 12- and 18-month PFS were 72.0% and 58.0%, respectively, and the median PFS was 26.8 months. In cohort 2, the confirmed overall response rate was 16% (primary endpoint), and the median PFS was 10.0 months (95% confidence interval, 7.0-17.9 months). Tumor histology, driver mutations, and immune-related biomarkers, including PD-L1 expression, thyroid-specific antibody levels, and CD8+ T-cell tumor infiltrate, did not correlate with response to therapy. Increased baseline peripheral blood monocytes and neutrophil to lymphocyte ratio were associated with a worse PFS in cohort 1. CONCLUSIONS Lenvatinib plus pembrolizumab may enhance the durability of lenvatinib monotherapy in lenvatinib-naïve patients. Furthermore, the addition of pembrolizumab may be a viable salvage therapy for patients who have progressed on lenvatinib.
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Affiliation(s)
- Jena D. French
- Division of Endocrinology, Metabolism, and Diabetes,
University of Colorado Anschutz Medical Campus, Aurora, Colorado
- Department of Medicine, University of Colorado Anschutz
Medical Campus, Aurora, Colorado
- University of Colorado Cancer Center, Aurora,
Colorado
| | - Bryan R. Haugen
- Division of Endocrinology, Metabolism, and Diabetes,
University of Colorado Anschutz Medical Campus, Aurora, Colorado
- Department of Medicine, University of Colorado Anschutz
Medical Campus, Aurora, Colorado
- University of Colorado Cancer Center, Aurora,
Colorado
| | - Francis P. Worden
- Department of Medicine, University of Michigan, Rogel
Cancer Center, Ann Arbor, Michigan
| | - Daniel W. Bowles
- University of Colorado Cancer Center, Aurora,
Colorado
- Division of Medical Oncology, University of Colorado
Denver, Aurora, Colorado
- Department of Medicine, University of Colorado Denver,
Aurora, Colorado
| | - Andrew G. Gianoukakis
- David Geffen School of Medicine at UCLA, Los Angeles,
California
- Lundquist Institute at Harbor-UCLA Medical Center,
Torrance, California
| | - Bhavana Konda
- Division of Medical Oncology, Department of Internal
Medicine, The Ohio State University Comprehensive Cancer Center, Columbus,
Ohio
| | - Ramona Dadu
- Department of Endocrine Neoplasia and Hormonal Disorders,
The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Eric J. Sherman
- David H. Koch Center for Cancer Care, Memorial Slone
Kettering Cancer Center, New York, New York
| | - Shaylene McCue
- Division of Clinical Trials and Biostatistics, Mayo
Clinic, Rochester, Minnesota
| | - Nathan R. Foster
- Division of Clinical Trials and Biostatistics, Mayo
Clinic, Rochester, Minnesota
| | - Yuri E. Nikiforov
- Department of Pathology, University of Pittsburgh School
of Medicine, Pittsburgh, Pennsylvania
| | - Ticiana D.J. Farias
- Department of Biomedical Informatics, University of
Colorado School of Medicine, Aurora, Colorado
| | - Paul J. Norman
- Department of Biomedical Informatics, University of
Colorado School of Medicine, Aurora, Colorado
- Department of Immunology and Microbiology, University of
Colorado School of Medicine, Aurora, Colorado
| | - Lori J. Wirth
- Massachusetts General Hospital, Boston,
Massachusetts
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Worden F, Rajkovic-Hooley O, Reynolds N, Milligan G, Zhang J. Real-world treatment patterns and clinical outcomes in patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) treated with first line lenvatinib monotherapy in the United States. Endocrine 2024; 84:663-669. [PMID: 38102498 PMCID: PMC11076410 DOI: 10.1007/s12020-023-03638-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 11/28/2023] [Indexed: 12/17/2023]
Abstract
PURPOSE Lenvatinib was approved for the treatment of patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) in the United States (US) in 2015. The main objective of the current study was to assess real-world clinical effectiveness in RAI-R DTC patients treated with first line lenvatinib monotherapy in the US. METHODS A retrospective chart review was conducted in RAI-R DTC patients who initiated lenvatinib monotherapy as first line treatment between February 2015 and September 2020. Anonymized data were abstracted by prescribing physicians from individual patient's electronic health records. Clinical outcomes included provider-reported real-world best overall response (rwBOR), real-world progression-free survival (rwPFS), and overall survival (OS). Time-to-event endpoints were assessed using Kaplan-Meier methods. RESULTS Our study included 308 RAI-R DTC patients treated with first line lenvatinib. At lenvatinib initiation, patients' median age was 60 years, 51.6% were female, and 26.0% of patients had an ECOG performance score of ≥2. Over the follow-up period, 32.5% of patients discontinued first line lenvatinib permanently, with others remaining on treatment. The median duration of lenvatinib therapy was 17.5 months overall. Provider-reported rwBOR (complete or partial response) to lenvatinib was 72.4%. Median rwPFS was 49.0 months. Estimated rwPFS rates at 24 and 48 months were 68.5% and 55.0%, respectively. Estimated OS rates at 24 and 72 months were 78.4% and 57.0%, respectively; median OS was not reached. CONCLUSION The current study reinforces the clinical effectiveness of first line lenvatinib as standard of care in patients with RAI-R DTC in real-world clinical practice in the US.
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Affiliation(s)
- Francis Worden
- University of Michigan Health System, Ann Arbor, MI, USA.
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Capdevila J, Krajewska J, Hernando J, Robinson B, Sherman SI, Jarzab B, Lin CC, Vaisman F, Hoff AO, Hitre E, Bowles DW, Williamson D, Levytskyy R, Oliver J, Keam B, Brose MS. Increased Progression-Free Survival with Cabozantinib Versus Placebo in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer Irrespective of Prior Vascular Endothelial Growth Factor Receptor-Targeted Therapy and Tumor Histology: A Subgroup Analysis of the COSMIC-311 Study. Thyroid 2024; 34:347-359. [PMID: 38062732 PMCID: PMC10951569 DOI: 10.1089/thy.2023.0463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2024]
Abstract
Background: Lenvatinib and sorafenib are standard of care first-line treatments for advanced, radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC). However, most patients eventually become treatment-resistant and require additional therapies. The phase 3 COSMIC-311 study investigated cabozantinib in patients with RAIR DTC who progressed on lenvatinib, sorafenib, or both and showed that cabozantinib provided substantial clinical benefit. Presented in this study is an analysis of COSMIC-311 based on prior therapy and histology. Methods: Patients were randomized 2:1 (stratification: prior lenvatinib [yes/no]; age [≤65, >65 years]) to oral cabozantinib (60 mg tablet/day) or matched placebo. Eligible patients received 1-2 prior vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors for DTC (lenvatinib or sorafenib required), had a confirmed DTC diagnosis, and were refractory to or ineligible for radioiodine therapy. For this analysis, progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by a blinded independent radiology committee were evaluated by prior therapy (lenvatinib only, sorafenib only, both) and histology (papillary, follicular, oncocytic, poorly differentiated). Results: Two hundred fifty-eight patients were randomized (170 cabozantinib/88 placebo) who previously received sorafenib only (n = 96), lenvatinib only (n = 102), or both (n = 60). The median follow-up was 10.1 months. The median PFS (months) with cabozantinib/placebo was 16.6/3.2 (sorafenib only: hazard ratio [HR] 0.13 [95% confidence interval, CI, 0.06-0.26]), 5.8/1.9 (lenvatinib only: HR 0.28 [95% CI 0.16-0.48]), and 7.6/1.9 (both: HR 0.27 [95% CI 0.13-0.54]). The ORR with cabozantinib/placebo was 21%/0% (sorafenib only), 4%/0% (lenvatinib only), and 8%/0% (both). Disease histology consisted of 150 papillary and 113 follicular, including 43 oncocytic and 36 poorly differentiated. The median PFS (months) with cabozantinib/placebo was 9.2/1.9 (papillary: HR 0.27 [95% CI 0.17-0.43]), 11.2/2.5 (follicular: HR 0.18 [95% CI 0.10-0.31]), 11.2/2.5 (oncocytic: HR 0.06 [95% CI 0.02-0.21]), and 7.4/1.8 (poorly differentiated: HR 0.18 [95% CI 0.08-0.43]). The ORR with cabozantinib/placebo was 15%/0% (papillary), 8%/0% (follicular), 11%/0% (oncocytic), and 9%/0% (poorly differentiated). Safety outcomes evaluated were consistent with those previously observed for the overall population. Conclusions: Results indicate that cabozantinib benefits patients with RAIR DTC, regardless of prior lenvatinib or sorafenib treatments or histology. Clinical Trial Registration Number: NCT03690388.
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Affiliation(s)
- Jaume Capdevila
- Gastrointestinal and Endocrine Tumor Unit, Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), IOB Quiron-Teknon, Barcelona, Spain
| | - Jolanta Krajewska
- Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland
| | - Jorge Hernando
- Vall d'Hebron University Hospital, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Bruce Robinson
- Department of Medicine, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Steven I. Sherman
- Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Barbara Jarzab
- Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland
| | - Chia-Chi Lin
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Fernanda Vaisman
- Department of Endocrinology, Instituto Nacional de Câncer, Rio de Janeiro, Brazil
| | - Ana O. Hoff
- Department of Endocrinology, Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, Brazil
| | - Erika Hitre
- Department of Medical Oncology, The Multidisciplinary Head and Neck Cancer Center, Országos Onkológiai Intézet, Budapest, Hungary
| | - Daniel W. Bowles
- Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Denise Williamson
- Department of Biostatistics, Exelixis, Inc., Alameda, California, USA
| | - Roman Levytskyy
- Department of Medical Affairs, Exelixis, Inc., Alameda, California, USA
| | - Jennifer Oliver
- Department of Clinical Development, Exelixis, Inc., Alameda, California, USA
| | - Bhumsuk Keam
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Marcia S. Brose
- Department of Medical Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Zhang LY, Cai SJ, Liang BY, Yan SY, Wang B, Li MY, Zhao WX. Efficacy of anlotinib combined with radioiodine to treat scalp metastasis of papillary thyroid cancer: A case report and review of literature. World J Clin Cases 2023; 11:2839-2847. [PMID: 37214573 PMCID: PMC10198115 DOI: 10.12998/wjcc.v11.i12.2839] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/27/2023] [Accepted: 03/22/2023] [Indexed: 04/25/2023] Open
Abstract
BACKGROUND Papillary thyroid cancer (PTC) is one of the well-differentiated thyroid tumors. Cutaneous metastasis from differentiated thyroid cancers occurs in < 1% of primary thyroid carcinomas but produces the worst survival prognosis. The multi-targeting tyrosine kinase inhibitor anlotinib has been approved to treat refractory advanced non-small-cell lung cancer as well as advanced soft-tissue and clear cell sarcomas in China. CASE SUMMARY In a patient with scalp metastasis caused by PTC, thyroid and skull metastasis tumor sizes were significantly reduced after a trial of neoadjuvant anlotinib therapy for 3 cycles. Anlotinib maintenance medication after thyroidectomy further reduced the metastatic skull tumor size thereby preventing the requirement for craniotomy. CONCLUSION The outcome of the present trial confirmed the potential of anlotinib therapy to treat scalp metastasis induced by PTC and point the way for the treatment of similar diseases in the future.
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Affiliation(s)
- Li-Yong Zhang
- Department of Thyroid Surgery, General Surgery, Minimal Invasive Center, The Training Center for Intraoperative Neurophysiologic Monitoring of Thyroid and Parathyroid, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China
| | - Shao-Jun Cai
- Department of Thyroid Surgery, General Surgery, Minimal Invasive Center, The Training Center for Intraoperative Neurophysiologic Monitoring of Thyroid and Parathyroid, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China
| | - Bo-Yan Liang
- Department of Thyroid Surgery, General Surgery, Minimal Invasive Center, The Training Center for Intraoperative Neurophysiologic Monitoring of Thyroid and Parathyroid, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China
| | - Shou-Yi Yan
- Department of Thyroid Surgery, General Surgery, Minimal Invasive Center, The Training Center for Intraoperative Neurophysiologic Monitoring of Thyroid and Parathyroid, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China
| | - Bo Wang
- Department of Thyroid Surgery, General Surgery, Minimal Invasive Center, The Training Center for Intraoperative Neurophysiologic Monitoring of Thyroid and Parathyroid, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China
| | - Meng-Yao Li
- Department of Thyroid Surgery, General Surgery, Minimal Invasive Center, The Training Center for Intraoperative Neurophysiologic Monitoring of Thyroid and Parathyroid, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China
| | - Wen-Xin Zhao
- Department of Thyroid Surgery, General Surgery, Minimal Invasive Center, The Training Center for Intraoperative Neurophysiologic Monitoring of Thyroid and Parathyroid, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China
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Peelay Z, Parekh D, Patil VM, Noronha V, Menon N, Prabhash K. Real-world analysis of the use of lenvatinib in differentiated thyroid cancers. Ecancermedicalscience 2023; 17:1500. [PMID: 36816785 PMCID: PMC9937066 DOI: 10.3332/ecancer.2023.1500] [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: 10/13/2022] [Indexed: 02/03/2023] Open
Abstract
Introduction Lenvatinib is one of the approved treatments for radioiodine-refractory differentiated thyroid cancers. However, there is very limited data from India on real-world efficacy and adverse events of Lenvatinib and hence this analysis was performed. Methods This was a retrospective analysis in which patients of radioiodine-refractory differentiated thyroid cancer as per the SELECT study criteria, who received lenvatinib, were selected for the study over the last 4 years. The baseline demographic characteristics, adverse events of lenvatinib, the date of progression and the date of overall survival (OS) were extracted from the electronic medical records of Tata Memorial Hospital. SPSS version 20 was used for analysis. Results The median starting dose of lenvatinib was 20 mg. Fifteen events for progression had occurred and the median progression-free survival (PFS) was 12.2 months [95% CI: 4.4-not available (NA)]. The events for OS analysis were 12. The median OS was 35.3 months (95% CI: 11.4-NA). There was no impact on starting dose on PFS or OS. Conclusion The real-world data of Lenvatinib suggest a lot of variability in the starting dose. In spite of this variability, the response rates and OS are similar to that noted in pivotal study. This suggests a case for need for more studies evaluating lower doses of Lenvatinib.
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Affiliation(s)
- Zoya Peelay
- Department of Medical Oncology, Tata Memorial Hospital, HBNI, Parel, Mumbai 400012, India
| | - Deevyashali Parekh
- Department of Medical Oncology, Tata Memorial Hospital, HBNI, Parel, Mumbai 400012, India
| | - Vijay M Patil
- Department of Medical Oncology, Tata Memorial Hospital, HBNI, Parel, Mumbai 400012, India
| | - Vanita Noronha
- Department of Medical Oncology, Tata Memorial Hospital, HBNI, Parel, Mumbai 400012, India
| | - Nandini Menon
- Department of Medical Oncology, Tata Memorial Hospital, HBNI, Parel, Mumbai 400012, India
| | - Kumar Prabhash
- Department of Medical Oncology, Tata Memorial Hospital, HBNI, Parel, Mumbai 400012, India
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Abstract
Molecular diagnostic testing has had a profound impact on the diagnosis and management of thyroid nodules and thyroid cancer. Based on the tremendous expansion of knowledge of the genomic landscape of thyroid cancer over the past few decades, tests have been developed, analyzed, modified, and implemented into clinical practice. Genomic testing of thyroid nodules to improve preoperative diagnosis has become an important component supporting decision-making in clinical care, reducing the need for diagnostic surgeries and improving accuracy of cancer risk assessment. In addition, a role for molecular testing of established thyroid cancers to assist in selection of therapeutic options for patients with advanced and/or progressive disease has been established. Research is ongoing to determine if molecular results should affect management of less aggressive forms of thyroid cancer earlier in clinical management. This review will outline the various commercial platforms for molecular diagnostics for nodules emphasizing their performance parameters and indications for use, as well as discuss the use of genomic analysis for progressive thyroid cancer and highlight opportunities for further research.
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Affiliation(s)
- Jennifer A Sipos
- Division of Endocrinology, Diabetes and Metabolism, The Ohio State University College of Medicine, Columbus, 43210, OH, USA
| | - Matthew D Ringel
- Division of Endocrinology, Diabetes and Metabolism, The Ohio State University College of Medicine, Co-leader, Cancer Biology Program, The Ohio State University Comprehensive Cancer Center, Columbus, 43210, OH, USA.
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Kim M, Jin M, Jeon MJ, Kim EY, Shin DY, Lim DJ, Kim BH, Kang HC, Kim WB, Shong YK, Kim HK, Kim WG. Lenvatinib Compared with Sorafenib as a First-Line Treatment for Radioactive Iodine-Refractory, Progressive, Differentiated Thyroid Carcinoma: Real-World Outcomes in a Multicenter Retrospective Cohort Study. Thyroid 2023; 33:91-99. [PMID: 35443825 DOI: 10.1089/thy.2022.0054] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Background: Sorafenib and lenvatinib have been widely adopted to treat radioactive iodine (RAI)-refractory differentiated thyroid carcinoma (DTC). However, limited data exist regarding a direct comparison of these tyrosine kinase inhibitors (TKIs). We aimed to evaluate the clinical efficacy and safety of two TKIs as first-line therapy in patients with distant metastatic or locally advanced, progressive, RAI-refractory DTC in real-world practice. Methods: In this multicenter, retrospective cohort study, we evaluated 136 patients with progressive distant metastatic or locally advanced, progressive, RAI-refractory DTC or poorly differentiated thyroid carcinoma (PDTC) who received first-line sorafenib or lenvatinib treatment. The primary outcome was progression-free survival (PFS). We also evaluated the objective response rate, disease-control rate, clinical benefit rate, and safety. Results: The median age of the patients was 68 years, and 35% (47/136) were male. Eighty and fifty-six patients were included in the sorafenib and lenvatinib groups, respectively. The median PFS was 13.3 months [95% confidence interval, CI, 9.9-18.1 months] in the sorafenib group and 35.3 months [CI, 18.2 months to upper limit not reported as the median was not reached] in the lenvatinib group (p = 0.001). A significantly prolonged PFS was observed in the lenvatinib group (compared with the sorafenib group) after adjusting for age, sex, pathology, disease-related symptom, lung-only metastasis, cumulative RAI dose, time from diagnosis, treatment duration, and longest diameter of the target lesion (hazard ratio = 0.34, CI, 0.19-0.60, p < 0.001). The partial response rate was 24% and 59% in the sorafenib and lenvatinib groups, respectively (p < 0.001). More common grade 3-4 adverse events were hypertension (16%, 9/56 vs. 1%, 1/80, p = 0.002) and proteinuria (32%, 18/56 vs. 0%, p < 0.001) in the lenvatinib group, and hand-foot skin reaction (24%, 19/80 vs. 4%, 2/56, p = 0.001) in the sorafenib group. Conclusion: In our study of Asian patients, first-line lenvatinib treatment of metastatic or locally advanced, progressive, RAI-refractory DTC or PDTC was associated with a longer PFS compared with sorafenib. However, severe hypertension and proteinuria were observed more frequently after lenvatinib treatment than after sorafenib treatment.
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Affiliation(s)
- Mijin Kim
- Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Meihua Jin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Min Ji Jeon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Eui Young Kim
- Department of Endocrinology, Dongnam Institute of Radiological and Medical Sciences Cancer Center, Busan, Republic of Korea
| | - Dong Yeob Shin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dong Jun Lim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Bo Hyun Kim
- Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Ho-Cheol Kang
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Won Bae Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Kee Shong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hee Kyung Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Won Gu Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Duke ES, Barone AK, Chatterjee S, Mishra-Kalyani PS, Shen YL, Isikwei E, Zhao H, Bi Y, Liu J, Rahman NA, Wearne E, Leighton JK, Stephenson M, Ojofeitimi I, Scepura B, Nair A, Pazdur R, Beaver JA, Singh H. FDA Approval Summary: Cabozantinib for Differentiated Thyroid Cancer. Clin Cancer Res 2022; 28:4173-4177. [PMID: 35679021 PMCID: PMC9529996 DOI: 10.1158/1078-0432.ccr-22-0873] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 05/10/2022] [Accepted: 05/24/2022] [Indexed: 12/14/2022]
Abstract
On September 17, 2021, the FDA approved cabozantinib (Cabometyx; Exelixis, Inc.) for the treatment of adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine (RAI)-refractory or ineligible. This is the first approval for patients with RAI-refractory locally advanced or metastatic DTC who have progressed following prior therapy and the first approval in pediatric patients with DTC. The approval was based on data from COSMIC-311 (Study XL184-311, NCT03690388), an international, randomized, double-blind trial in which patients with locally advanced or metastatic RAI-refractory DTC that progressed during or following treatment with at least one VEGFR-targeting tyrosine kinase inhibitor were treated with either cabozantinib 60 mg orally once daily (N = 170) or placebo with best supportive care (N = 88). The primary efficacy outcome measures were progression-free survival (PFS) and overall response rate (ORR) by blinded independent central review per RECIST 1.1. The median PFS was 11.0 months [95% confidence interval (CI), 7.4-13.8] in the cabozantinib arm compared with 1.9 months (95% CI, 1.9-3.7) in the control arm, with an HR of 0.22 (95% CI, 0.15-0.31). The endpoint of ORR was not met. No new safety signals were identified with the exception of hypocalcemia, which was added as a warning in the product labeling.
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Affiliation(s)
| | | | | | | | | | | | - Hong Zhao
- Center for Drug Evaluation and Research
| | - Youwei Bi
- Center for Drug Evaluation and Research
| | - Jiang Liu
- Center for Drug Evaluation and Research
| | | | | | | | | | | | | | | | - Richard Pazdur
- Center for Drug Evaluation and Research,Oncology Center of Excellence, U.S. Food and Drug Administration
| | - Julia A. Beaver
- Center for Drug Evaluation and Research,Oncology Center of Excellence, U.S. Food and Drug Administration
| | - Harpreet Singh
- Center for Drug Evaluation and Research,Oncology Center of Excellence, U.S. Food and Drug Administration
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10
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Masaki C, Sugino K, Akaishi J, Hames KY, Tomoda C, Suzuki A, Matsuzu K, Ohkuwa K, Kitagawa W, Nagahama M, Ito K. Successful dose escalation of lenvatinib for thyroid cancer after disease progression. Endocrine 2022; 78:77-84. [PMID: 35737285 DOI: 10.1007/s12020-022-03117-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 06/14/2022] [Indexed: 11/26/2022]
Abstract
PURPOSE Lenvatinib is started at a standard dose, continuing with dose reduction and interruption, balancing between efficacy and adverse events (AEs). Because few drugs are available for thyroid cancer, efforts for continuing treatment with one agent, such as "dose escalation (DE)", are made. The dose is increased, aiming to regain the anti-tumor effect after dose reduction. The effects of lenvatinib DE in differentiated thyroid carcinoma (DTC) patients are reported. PATIENTS AND METHODS The efficacy of lenvatinib DE in DTC patients using the serum thyroglobulin (Tg) level and management of AEs was investigated. RESULTS A total of 70 DE episodes in 33 patients were investigated. The median increased dose was 2.0 (1.0-14.0) mg, increased from 8.6 (2-16) mg to 10.1 (6-24) mg. The serum Tg level decreased in 53 DE episodes. Though the serum Tg level in 17 DE episodes was not decreased, the Tg rate of increase was decreased in 7 of these DE episodes using the Tg-doubling rate. Overall, clinical benefit was seen in 60 (86%) DE episodes. AEs that could not be controlled after DEs were seen in only 16% of cases. No intolerable AEs were observed in patients who received more drug holidays at the time of DEs compared to two times before the DEs. CONCLUSION DE may become one of the standard treatment strategies after disease progression if AEs are well managed. Drug holidays may be a key for successfully controlling AEs with DE. DE can be useful for controlling progressive disease with increasing Tg levels.
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Affiliation(s)
- Chie Masaki
- Department of Surgery, Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan.
| | - Kiminori Sugino
- Department of Surgery, Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Junko Akaishi
- Department of Surgery, Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Kiyomi Y Hames
- Department of Surgery, Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Chisato Tomoda
- Department of Surgery, Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Akifumi Suzuki
- Department of Surgery, Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Kenichi Matsuzu
- Department of Surgery, Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Keiko Ohkuwa
- Department of Surgery, Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Wataru Kitagawa
- Department of Surgery, Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Mitsuji Nagahama
- Department of Surgery, Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Koichi Ito
- Department of Surgery, Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
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11
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Li J, Zhang Y, Sun F, Xing L, Sun X. Towards an era of precise diagnosis and treatment: Role of novel molecular modification-based imaging and therapy for dedifferentiated thyroid cancer. Front Endocrinol (Lausanne) 2022; 13:980582. [PMID: 36157447 PMCID: PMC9493193 DOI: 10.3389/fendo.2022.980582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 08/04/2022] [Indexed: 12/07/2022] Open
Abstract
Dedifferentiated thyroid cancer is the major cause of mortality in thyroid cancer and is difficult to treat. Hence, the essential molecular mechanisms involved in dedifferentiation should be thoroughly investigated. Several studies have explored the biomolecular modifications of dedifferentiated thyroid cancer such as DNA methylation, protein phosphorylation, acetylation, ubiquitination, and glycosylation and the new targets for radiological imaging and therapy in recent years. Novel radionuclide tracers and drugs have shown attractive potential in the early diagnosis and treatment of dedifferentiated thyroid cancer. We summarized the updated molecular mechanisms of dedifferentiation combined with early detection by molecular modification-based imaging to provide more accurate diagnosis and novel therapeutics in the management of dedifferentiated thyroid cancer.
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Affiliation(s)
- Jing Li
- Department of Graduate, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
- Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Yingjie Zhang
- Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Fenghao Sun
- Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Ligang Xing
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Xiaorong Sun
- Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
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12
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Pharmacoepidemiology for oncology clinical practice: Foundations, state of the art and perspectives. Therapie 2022; 77:229-240. [DOI: 10.1016/j.therap.2021.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 08/23/2021] [Indexed: 11/20/2022]
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13
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2-[18F]FDG PET in the Management of Radioiodine Refractory Differentiated Thyroid Cancer in the Era of Thyrosin-Kinases Inhibitors: A Real-Life Retrospective Study. Diagnostics (Basel) 2022; 12:diagnostics12020506. [PMID: 35204596 PMCID: PMC8870858 DOI: 10.3390/diagnostics12020506] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/02/2022] [Accepted: 02/09/2022] [Indexed: 02/05/2023] Open
Abstract
Purpose To evaluate the role of 2-[18F]FDGPET/CT in the follow-up of radioiodine refractory thyroid cancer (RR-TC). Methods Forty-six 2-[18F]FDGPET/CT scans from 14 RR-TC patients were considered. Thyroid function tests: thyroglobulin (Tg), levothyroxine (LT4), and tyrosine-kinases inhibitors (TKIs) assumptions were recorded. Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated from each scan and correlated with clinical parameters and the overall survival (OS). Results Baseline TLG and MTV predicted OS (p = 0.027 and p = 0.035), and negative correlation with OS was also confirmed when the same parameters were measured in follow-up scans (p = 0.015 and p = 0.021). Tg also correlated with the OS; (p = 0.014; p = 0.019 and p = 0.009). However, TLG and MTV were not significantly correlated with Tg levels. MTV and TLG variation in time were reduced during TKI therapy (p = 0.045 and p = 0.013). Conclusions 2-[18F]FDGPET/CT confirmed its prognostic role at the first assessment and during the follow-up of RR-TC patients. 2-[18F]FDGPET/CT parameters seem at least partially independent from Tg. TKI therapy resulted in a measurable effect on the variation of 2-[18F]FDGPET/CT parameters over time.
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14
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Li L, Cheng L, Sa R, Qiu X, Chen L. Real-world insights into the efficacy and safety of tyrosine kinase inhibitors against thyroid cancers. Crit Rev Oncol Hematol 2022; 172:103624. [PMID: 35150866 DOI: 10.1016/j.critrevonc.2022.103624] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 01/29/2022] [Accepted: 02/07/2022] [Indexed: 01/01/2023] Open
Abstract
Based on clinical trials demonstrating favorable short-term efficacy and tolerable toxicity, several tyrosine kinase inhibitors have been approved for treating locally recurrent or metastatic, progressive radioiodine-refractory differentiated thyroid cancer, BRAFV600E-mutant anaplastic thyroid cancer, and advanced or progressive medullary thyroid cancer. Longer term efficacy and safety of these treatments have been investigated in multiple real-world studies, demonstrating indispensable complementary value. Hereby, we summarize data from a total of 27 real-world studies with a focus on long-term survival data and rare but life-threatening adverse effects. An overall picture of current real-world study was drawn, and integrated experience of multiple centers would be helpful to clinical practice and further research.
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Affiliation(s)
- Lingyu Li
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China; Shanghai Jiao Tong University School of Medicine, 227, South Chongqing Road, Shanghai 200023, China
| | - Lin Cheng
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
| | - Ri Sa
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China; Shanghai Jiao Tong University School of Medicine, 227, South Chongqing Road, Shanghai 200023, China
| | - Xian Qiu
- Shanghai Jiao Tong University School of Medicine, 227, South Chongqing Road, Shanghai 200023, China
| | - Libo Chen
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China; Shanghai Jiao Tong University School of Medicine, 227, South Chongqing Road, Shanghai 200023, China.
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15
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Kaae AC, Kreissl MC, Krüger M, Infanger M, Grimm D, Wehland M. Kinase-Inhibitors in Iodine-Refractory Differentiated Thyroid Cancer-Focus on Occurrence, Mechanisms, and Management of Treatment-Related Hypertension. Int J Mol Sci 2021; 22:12217. [PMID: 34830100 PMCID: PMC8623313 DOI: 10.3390/ijms222212217] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 11/08/2021] [Accepted: 11/09/2021] [Indexed: 12/26/2022] Open
Abstract
Differentiated thyroid cancer (DTC) usually has a good prognosis when treated conventionally with thyroidectomy, radioactive iodine (RAI) and thyroid-stimulating hormone suppression, but some tumors develop a resistance to RAI therapy, requiring alternative treatments. Sorafenib, lenvatinib and cabozantinib are multikinase inhibitors (MKIs) approved for the treatment of RAI-refractory DTC. The drugs have been shown to improve progression-free survival (PFS) and overall survival (OS) via the inhibition of different receptor tyrosine kinases (RTKs) that are involved in tumorigenesis and angiogenesis. Both sorafenib and lenvatinib have been approved irrespective of the line of therapy for the treatment of RAI-refractory DTC, whereas cabozantinib has only been approved as a second-line treatment. Adverse effects (AEs) such as hypertension are often seen with MKI treatment, but are generally well manageable. In this review, current clinical studies will be discussed, and the toxicity and safety of sorafenib, lenvatinib and cabozantinib treatment will be evaluated, with a focus on AE hypertension and its treatment options. In short, treatment-emergent hypertension (TE-HTN) occurs with all three drugs, but is usually well manageable and leads only to a few dose modifications or even discontinuations. This is emphasized by the fact that lenvatinib is widely considered the first-line drug of choice, despite its higher rate of TE-HTN.
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Affiliation(s)
- Anne Christine Kaae
- Department of Biomedicine, Aarhus University, Ole Worms Allé 4, 8000 Aarhus, Denmark; (A.C.K.); (D.G.)
| | - Michael C. Kreissl
- Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany;
| | - Marcus Krüger
- Department of Microgravity and Translational Regenerative Medicine, Otto von Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany; (M.K.); (M.I.)
| | - Manfred Infanger
- Department of Microgravity and Translational Regenerative Medicine, Otto von Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany; (M.K.); (M.I.)
- Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany
| | - Daniela Grimm
- Department of Biomedicine, Aarhus University, Ole Worms Allé 4, 8000 Aarhus, Denmark; (A.C.K.); (D.G.)
- Department of Microgravity and Translational Regenerative Medicine, Otto von Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany; (M.K.); (M.I.)
- Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany
| | - Markus Wehland
- Department of Microgravity and Translational Regenerative Medicine, Otto von Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany; (M.K.); (M.I.)
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16
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Ratajczak M, Gaweł D, Godlewska M. Novel Inhibitor-Based Therapies for Thyroid Cancer-An Update. Int J Mol Sci 2021; 22:11829. [PMID: 34769260 PMCID: PMC8584403 DOI: 10.3390/ijms222111829] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/27/2021] [Accepted: 10/28/2021] [Indexed: 12/16/2022] Open
Abstract
Thyroid cancers (TCs) are the most common tumors of the endocrine system and a constant rise in the number of TC cases has been observed for the past few decades. TCs are one of the most frequent tumors in younger adults, especially in women, therefore early diagnosis and effective therapy are especially important. Ultrasonography examination followed by fine needle biopsy have become the gold standard for diagnosis of TCs, as these strategies allow for early-stage detection and aid accurate qualification for further procedures, including surgical treatment. Despite all the advancements in detection and treatment of TCs, constant mortality levels are still observed. Therefore, a novel generation line of targeted treatment strategies is being developed, including personalized therapies with kinase inhibitors. Recent molecular studies on TCs demonstrate that kinase inhibitor-based therapies might be considered as the most promising. In the past decade, new kinase inhibitors with different mechanisms of action have been reported and approved for clinical trials. This review presents an up-to-date picture of new approaches and challenges of inhibitor-based therapies in treatment of TCs, focusing on the latest findings reported over the past two years.
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Affiliation(s)
- Maciej Ratajczak
- Centre of Postgraduate Medical Education, Department of Endocrinology, Marymoncka 99/103, 01-813 Warsaw, Poland;
| | - Damian Gaweł
- Centre of Postgraduate Medical Education, Department of Immunohematology, Marymoncka 99/103, 01-813 Warsaw, Poland
- Centre of Postgraduate Medical Education, Department of Biochemistry and Molecular Biology, Marymoncka 99/103, 01-813 Warsaw, Poland
| | - Marlena Godlewska
- Centre of Postgraduate Medical Education, Department of Biochemistry and Molecular Biology, Marymoncka 99/103, 01-813 Warsaw, Poland
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17
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Ferrari SM, Elia G, Ragusa F, Paparo SR, Mazzi V, Miccoli M, Galdiero MR, Varricchi G, Foddis R, Guglielmi G, Spinelli C, La Motta C, Benvenga S, Antonelli A, Fallahi P. Lenvatinib: an investigational agent for the treatment of differentiated thyroid cancer. Expert Opin Investig Drugs 2021; 30:913-921. [PMID: 34428101 DOI: 10.1080/13543784.2021.1972971] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Differentiated thyroid cancer (DTC; >90% of all TCs) derives from follicular cells. Surgery is the main therapeutic strategy, and radioiodine (RAI) is administered after thyroidectomy. When DTC progresses, it does not respond to RAI and thyroid-stimulating hormone (TSH)-suppressive thyroid hormone treatment, and other therapies (i.e. surgery, external beam radiation therapy and chemotherapy) do not lead to a better survival. Thanks to the understanding of the molecular pathways involved in TC progression, important advances have been done. Lenvatinib is a multitargeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRα, RET, and KIT signaling networks implicated in tumor angiogenesis, approved in locally recurrent or metastatic, progressive, RAI-refractory DTC. Unmet needs regarding the patient clinical therapy responsiveness in aggressive RAI-refractory DTC still remain. AREAS COVERED We provide an overview from the literature of in vitro, in vivo and real-life studies regarding lenvatinib as an investigational agent for the treatment of aggressive TC. EXPERT OPINION According to the SELECT trial, the treatment should be initiated with a dosage of 24 mg/day, subsequently decreasing it in relation to the side effects. The decision making process in patients with aggressive RAI-refractory DTC should be personalized and the potential toxicity should be properly managed.
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Affiliation(s)
| | - Giusy Elia
- Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy
| | - Francesca Ragusa
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | | | - Valeria Mazzi
- Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy
| | - Mario Miccoli
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Maria Rosaria Galdiero
- Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy; WAO Center of Excellence, Naples, Italy; Institute of Experimental Endocrinology and Oncology "G. Salvatore" (IEOS), National Research Council (CNR),Naples, Italy
| | - Gilda Varricchi
- Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy; WAO Center of Excellence, Naples, Italy; Institute of Experimental Endocrinology and Oncology "G. Salvatore" (IEOS), National Research Council (CNR),Naples, Italy
| | - Rudy Foddis
- Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Giovanni Guglielmi
- U.O. Medicina Preventiva Del Lavoro, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Claudio Spinelli
- Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy
| | | | - Salvatore Benvenga
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.,Master Program on Childhood, Adolescent and Women's Endocrine Health, University of Messina, Messina, Italy.,Interdepartmental Program of Molecular and Clinical Endocrinology and Women's Endocrine Health, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy
| | - Alessandro Antonelli
- Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy
| | - Poupak Fallahi
- Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
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Multikinase inhibitors for the treatment of radioiodine refractory thyroid cancer: what have we learned from the 'real-world' experience? Curr Opin Oncol 2021; 33:3-8. [PMID: 33060402 DOI: 10.1097/cco.0000000000000693] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
PURPOSE OF REVIEW Several molecularly targeted drugs for treating radioiodine resistant differentiated thyroid carcinomas (RAIR-DTC) have been identified. Among these, sorafenib and lenvatinib have been approved for clinical use in many countries. The present review will analyze efficacy and safety 'real-world' data (RWD) emerging after their commercialization. RECENT FINDINGS RWDs confirmed sorafenib and lenvatinib efficacy in terms of progression-free survival and, perhaps, overall survival improvement in patients with RAIR-DTC. Lenvatinib performance in RWDs appeared somehow lower than in randomized clinical trials (RCT), probably because the decision to start treatment in 'real life' was made when patients were in worse clinical conditions than in RCTs. Concerning safety, RWD studies corroborated RCT evidence of elevated overall and serious adverse event incidence. Notably, adverse events were manageable in most cases with appropriate treatment or dose reduction/interruption, so that the need for definitive withdrawal was limited. The suitability of multikinase inhibitors (MKI) as salvage therapy in RAIR-DTCs was also confirmed by RWD experience, at least for lenvatinib in the second-line setting. SUMMARY RWD analysis has corroborated RCT results in terms of MKI efficacy for both first-line and salvage treatment in patients with RAIR-DTC. The safety profiles emerging from RWDs seem to justify the caution recommended by most scientific guidelines.
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19
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Brose MS, Robinson B, Sherman SI, Krajewska J, Lin CC, Vaisman F, Hoff AO, Hitre E, Bowles DW, Hernando J, Faoro L, Banerjee K, Oliver JW, Keam B, Capdevila J. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2021; 22:1126-1138. [PMID: 34237250 DOI: 10.1016/s1470-2045(21)00332-6] [Citation(s) in RCA: 137] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/25/2021] [Accepted: 05/27/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND Patients with radioiodine-refractory differentiated thyroid cancer (DTC) previously treated with vascular endothelial growth factor receptor (VEGFR)-targeted therapy have aggressive disease and no available standard of care. The aim of this study was to evaluate the tyrosine kinase inhibitor cabozantinib in this patient population. METHODS In this global, randomised, double-blind, placebo-controlled, phase 3 trial, patients aged 16 years and older with radioiodine-refractory DTC (papillary or follicular and their variants) and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (2:1) to oral cabozantinib (60 mg once daily) or matching placebo, stratified by previous lenvatinib treatment and age. The randomisation scheme used stratified permuted blocks of block size six and an interactive voice-web response system; both patients and investigators were masked to study treatment. Patients must have received previous lenvatinib or sorafenib and progressed during or after treatment with up to two VEGFR tyrosine kinase inhibitors. Patients receiving placebo could cross over to open-label cabozantinib on disease progression confirmed by blinded independent radiology committee (BIRC). The primary endpoints were objective response rate (confirmed response per Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) in the first 100 randomly assigned patients (objective response rate intention-to-treat [OITT] population) and progression-free survival (time to earlier of disease progression per RECIST version 1.1 or death) in all patients (intention-to-treat [ITT] population), both assessed by BIRC. This report presents the primary objective response rate analysis and a concurrent preplanned interim progression-free survival analysis. The study is registered with ClinicalTrials.gov, NCT03690388, and is no longer enrolling patients. FINDINGS Between Feb 27, 2019, and Aug 18, 2020, 227 patients were assessed for eligibility, of whom 187 were enrolled from 164 clinics in 25 countries and randomly assigned to cabozantinib (n=125) or placebo (n=62). At data cutoff (Aug 19, 2020) for the primary objective response rate and interim progression-free survival analyses, median follow-up was 6·2 months (IQR 3·4-9·2) for the ITT population and 8·9 months (7·1-10·5) for the OITT population. An objective response in the OITT population was achieved in ten (15%; 99% CI 5·8-29·3) of 67 patients in the cabozantinib group versus 0 (0%; 0-14·8) of 33 in the placebo (p=0·028) but did not meet the prespecified significance level (α=0·01). At interim analysis, the primary endpoint of progression-free survival was met in the ITT population; cabozantinib showed significant improvement in progression-free survival over placebo: median not reached (96% CI 5·7-not estimable [NE]) versus 1·9 months (1·8-3·6); hazard ratio 0·22 (96% CI 0·13-0·36; p<0·0001). Grade 3 or 4 adverse events occurred in 71 (57%) of 125 patients receiving cabozantinib and 16 (26%) of 62 receiving placebo, the most frequent of which were palmar-plantar erythrodysaesthesia (13 [10%] vs 0), hypertension (11 [9%] vs 2 [3%]), and fatigue (ten [8%] vs 0). Serious treatment-related adverse events occurred in 20 (16%) of 125 patients in the cabozantinib group and one (2%) of 62 in the placebo group. There were no treatment-related deaths. INTERPRETATION Our results show that cabozantinib significantly prolongs progression-free survival and might provide a new treatment option for patients with radioiodine-refractory DTC who have no available standard of care. FUNDING Exelixis.
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Affiliation(s)
- Marcia S Brose
- Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
| | - Bruce Robinson
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Steven I Sherman
- Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jolanta Krajewska
- Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland
| | - Chia-Chi Lin
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | | | - Ana O Hoff
- Department of Endocrinology, Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, Brazil
| | - Erika Hitre
- Department of Medical Oncology and Clinical Pharmacology "B", Országos Onkológiai Intézet, Budapest, Hungary
| | - Daniel W Bowles
- Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Jorge Hernando
- Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | | | | | - Bhumsuk Keam
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Jaume Capdevila
- Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain
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20
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Clinical Indications for Treatment with Multi-Kinase Inhibitors in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer. Cancers (Basel) 2021; 13:cancers13092279. [PMID: 34068664 PMCID: PMC8126102 DOI: 10.3390/cancers13092279] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 05/05/2021] [Accepted: 05/07/2021] [Indexed: 12/21/2022] Open
Abstract
Differentiated thyroid cancer is usually a slow-growing disease, even if the patients develop distant metastasis. For recurrent or metastatic disease, radioactive iodine therapy is a standard treatment. However, the disease gradually progresses in some of the patients and can ultimately develop into life-threatening conditions. For patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RR-DTC), multi-kinase inhibitors (MKIs) including sorafenib and lenvatinib prolonged progression-free survival compared with placebo in pivotal randomized phase 3 trials, although the benefit in overall survival has not been clearly confirmed, possibly because the patients who received placebo were permitted to cross-over to lenvatinib upon disease progression. Moreover, the adverse events related to MKIs were not negligible. Therefore, the optimal timing of MKI initiation has long been controversial, and physicians should consider various patient and disease factors. Herein, we comprehensively review the clinical factors that can be helpful in determining the initiation of MKIs for patients with RR-DTC.
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21
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Verburg FA, Amthauer H, Binse I, Brink I, Buck A, Darr A, Dierks C, Koch C, König U, Kreissl MC, Luster M, Reuter C, Scheidhauer K, Willenberg HS, Zielke A, Schott M. Questions and Controversies in the Clinical Application of Tyrosine Kinase Inhibitors to Treat Patients with Radioiodine-Refractory Differentiated Thyroid Carcinoma: Expert Perspectives. Horm Metab Res 2021; 53:149-160. [PMID: 33652491 PMCID: PMC7932822 DOI: 10.1055/a-1380-4154] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Notwithstanding regulatory approval of lenvatinib and sorafenib to treat radioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC), important questions and controversies persist regarding this use of these tyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiary referral centers convened to identify and explore such issues; this paper summarizes their discussions. One challenge is determining when to start TKI therapy. Decision-making should be shared between patients and multidisciplinary caregivers, and should consider tumor size/burden, growth rate, and site(s), the key drivers of RAI-R DTC morbidity and mortality, along with current and projected tumor-related symptomatology, co-morbidities, and performance status. Another question involves choice of first-line TKIs. Currently, lenvatinib is generally preferred, due to greater increase in progression-free survival versus placebo treatment and higher response rate in its pivotal trial versus that of sorafenib; additionally, in those studies, lenvatinib but not sorafenib showed overall survival benefit in subgroup analysis. Whether recommended maximum or lower TKI starting doses better balance anti-tumor effects versus tolerability is also unresolved. Exploratory analyses of lenvatinib pivotal study data suggest dose-response effects, possibly favoring higher dosing; however, results are awaited of a prospective comparison of lenvatinib starting regimens. Some controversy surrounds determination of net therapeutic benefit, the key criterion for continuing TKI therapy: if tolerability is acceptable, overall disease control may justify further treatment despite limited but manageable progression. Future research should assess potential guideposts for starting TKIs; fine-tune dosing strategies and further characterize antitumor efficacy; and evaluate interventions to prevent and/or treat TKI toxicity, particularly palmar-plantar erythrodysesthesia and fatigue.
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Affiliation(s)
- Frederik A. Verburg
- Department of Nuclear Medicine, University Hospital Marburg, Marburg,
Germany
- Erasmus Medical Center, Department of Radiology and Nuclear Medicine,
Rotterdam, The Netherlands
- Correspondence Frederik A. Verburg M.D., PhD. Department of Radiology and Nuclear MedicineErasmus Medical CenterDoctor Molewaterplein 403015 GD RotterdamThe Netherlands+31 10 704 0 704
| | - Holger Amthauer
- Charité - Universitätsmedizin Berlin, Freie
Universität Berlin, Humboldt-Universität zu Berlin, and Berlin
Institute of Health, Department of Nuclear Medicine, Berlin,
Germany
| | - Ina Binse
- Department of Nuclear Medicine, University Clinic Essen, Essen,
Germany
| | - Ingo Brink
- Department of Medical Diagnostics and Therapy, Ernst von Bergmann
Hospital Potsdam, Potsdam, Germany
| | - Andreas Buck
- Department of Nuclear Medicine, University Hospital Würzburg,
Würzburg, Germany
| | - Andreas Darr
- Department of Nuclear Medicine, University Hospital Jena, Jena,
Germany
| | - Christine Dierks
- Department of Medical Oncology, University Hospital Freiburg, Freiburg,
Germany
| | - Christine Koch
- Department of Gastroenterology, Hepatology, and Endocrinology,
University Clinic Frankfurt, Frankfurt Am Main, Germany
| | - Ute König
- Department of Gastroenterology and Endocrinology, University of
Göttingen, Göttingen, Germany
| | - Michael C. Kreissl
- Division of Nuclear Medicine, Department of Radiology and Nuclear
Medicine, Otto von Guericke University Magdeburg, Magdeburg,
Germany
| | - Markus Luster
- Department of Nuclear Medicine, University Hospital Marburg, Marburg,
Germany
| | - Christoph Reuter
- Department of Palliative Care, Hannover Medical School, Hannover,
Germany
| | - Klemens Scheidhauer
- Interdisclipinary Endocrine Center, Technical University of Munich,
Munich, Germany
| | - Holger Sven Willenberg
- Division of Endocrinology and Metabolism, Medical University of
Rostock, Rostock, Germany
| | - Andreas Zielke
- Department of Endocrine Surgery, Diakonie Klinikum Stuttgart,
Stuttgart, Germany
| | - Matthias Schott
- Division of Endocrinology, University Hospital Düsseldorf,
Düsseldorf, Germany
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22
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Feinberg BA, Zettler ME, Klink AJ, Lee CH, Gajra A, Kish JK. Comparison of Solid Tumor Treatment Response Observed in Clinical Practice With Response Reported in Clinical Trials. JAMA Netw Open 2021; 4:e2036741. [PMID: 33630085 PMCID: PMC7907955 DOI: 10.1001/jamanetworkopen.2020.36741] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
IMPORTANCE In clinical trials supporting the regulatory approval of oncology drugs, solid tumor response is assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Calculation of RECIST-based responses requires sequential, timed imaging data, which presents challenges to the method's application in real-world evidence research. OBJECTIVE To evaluate the feasibility and validity of a novel real-world RECIST method in assessing tumor burden associated with therapy for a large heterogeneous patient population undergoing treatment in routine clinical practice. DESIGN, SETTING, AND PARTICIPANTS This cohort study used physician-abstracted data pooled from retrospective, multisite electronic health record (EHR) review studies of patients treated with anticancer drugs at US oncology practices from 2014 through 2017. Included patients were receiving first-line treatment for thyroid cancer, breast cancer, or metastatic melanoma. Data were analyzed from March through August 2020. EXPOSURES Undergoing treatment with immunotherapy or targeted therapy. MAIN OUTCOMES AND MEASURES Tumor response was classified according to RECIST guidelines (ie, change in sum diameter of target lesions) post hoc with measurements derived from imaging scans and reports. RESULTS Among 1308 completed electronic case report forms, 956 forms (73.1%) had adequate data to classify real-world RECIST response. The greatest difference between physician-recorded responses and real-world RECIST-based responses was found in the proportion of complete responses: 118 responses (12.3%) vs 46 responses (4.8%) (P < .001). Among 609 patients in the metastatic melanoma population, complete responses were reported in 112 physician-recorded responses (18.4%) vs 44 real-world RECIST-based responses (7.2%) (P < .001), compared with 11 of 247 responses (4.5%) to 31 of 192 responses (16.1%) across pivotal trials of the same melanoma therapies. CONCLUSIONS AND RELEVANCE These findings suggest that comparing tumor lesion sizes and categorizing treatment response according to RECIST guidelines may be feasible using real-world data. This study found that physician-recorded assessments were associated with overestimation of treatment response, with the largest overestimation among complete responses. Real-world RECIST-based assessments were associated with better approximations of tumor response reported in clinical trials compared with those reported in EHRs.
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Affiliation(s)
| | | | | | - Choo H Lee
- Cardinal Health Specialty Solutions, Dublin, Ohio
| | - Ajeet Gajra
- Cardinal Health Specialty Solutions, Dublin, Ohio
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23
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Ringel MD. New Horizons: Emerging Therapies and Targets in Thyroid Cancer. J Clin Endocrinol Metab 2021; 106:e382-e388. [PMID: 32977343 PMCID: PMC7765632 DOI: 10.1210/clinem/dgaa687] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 09/23/2020] [Indexed: 12/21/2022]
Abstract
The treatment of patients with progressive metastatic follicular cell-derived and medullary thyroid cancers that do not respond to standard therapeutic modalities presents a therapeutic challenge. As a deeper understanding of the molecular drivers for these tumors has occurred and more potent and specific compounds are developed, the number of Food and Drug Administration (FDA)-approved treatments for thyroid cancer has expanded. In addition, with the advent of disease-agnostic target-directed FDA approvals an ever-broadening number of therapeutic options are available for clinicians and patients. However, to date, complete remissions are rare, the average durations of response are relatively modest, and toxicities are common. These factors accentuate the need for further understanding of the mechanisms of resistance that result in treatment failures, the development of biomarkers that can improve patient selection for treatment earlier in the disease process, and the continued need for new therapeutic strategies. In this article, recent approvals relevant to thyroid cancer will be discussed along with selected new potential avenues that might be exploited for future therapies.
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Affiliation(s)
- Matthew D Ringel
- Division of Endocrinology, Diabetes, and Metabolism and Cancer Biology Program, The Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, Ohio
- Correspondence and Reprint Requests: Matthew D. Ringel, MD, McCampbell Hall South, Room 565, 1581 Dodd Drive, Columbus, OH 43210, USA. E-mail:
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24
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Correlation between F18-FDG PET/CT Imaging and BRAF V600E Genetic Mutation for the Early Assessment of Treatment Response in Papillary Thyroid Cancers. J Pers Med 2020; 10:jpm10020052. [PMID: 32575591 PMCID: PMC7354584 DOI: 10.3390/jpm10020052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 06/11/2020] [Accepted: 06/18/2020] [Indexed: 11/25/2022] Open
Abstract
In thyroid neoplastic pathology, the BRAF V600E mutation is shown to be involved in the oncogenesis of papillary thyroid cancer and its subtypes. The purpose of this study is to evaluate the correlation between the mutation of the BRAF V600E oncogene and the pathological standardized uptake values (SUV) at the F18-fluorodeoxyglucose (F18-FDG) positron emission tomography/computed tomography (PET/CT) evaluation, for a group of 20 patients with radically treated (total thyroidectomy and radioiodine therapy) papillary thyroid cancer, with subclinical persistent disease, at 6 months after the initial treatment. We analyzed the correlations between the values of SUV and the presence of the BRAF mutation as well with other prognostic factors such as stage, age, specific tumor markers (thyroglobulin and anti-thyroglobulin), extrathyroid extension, the presence of metastatic lymph nodes or distant metastasis. The value of SUV in the case of BRAF+ (positive) patients was higher than in the negative ones, but without statistical significance, thus, the values of the SUV cannot be a predictable factor for the presence of the genetic mutation. There was a statistically significant correlation in BRAF+ subgroup between the SUV values and the positive resection limit following surgery, showing a higher SUV value in the PET/CT evaluation. No correlation was observed between the aforementioned prognostic factors involved in papillary thyroid cancer and the BRAF V600E mutation.
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