This study evaluated the occurrence of apatinib-induced hypertension and its impact on the prognosis of patients with solid tumors. A retrospective cohort study with prospective follow-up was conducted on 769 patients treated with apatinib from 2014 to 2021 across three hospitals. Patients were categorized into hypertension and non-hypertension groups. The primary outcome was overall survival (OS), with progression-free survival (PFS) as a secondary outcome. Apatinib-induced hypertension occurred in 33.3% of patients and was associated with significantly longer OS (HR 0.40, 95% CI [0.37-0.48], p < 0.0001) and PFS (HR 0.41, 95% CI [0.35-0.49], p < 0.001). Subgroup analysis confirmed these findings in all cancer types, except for PFS in non-small cell lung cancer. Hypertension may serve as a predictive biomarker for improved anti-tumor efficacy.

Vascular endothelial growth factor (VEGF) gene polymorphisms are associated with the response to pharmaceutical therapy in many cancers. This study aimed to investigate the effects of VEGF gene polymorphisms in esophageal squamous cell carcinoma patients receiving pharmaceutical therapy.

This literature-based meta-analysis was performed with keywords related to VEGF gene polymorphisms and clinical response in esophageal squamous carcinoma patients receiving pharmaceutical therapy (including 5-FU, cisplatin, oxaliplatin, and calcium folinate). After a series of bias grading analyses and DerSimonian-Laird method analysis, odds ratios and 95% confidence intervals were calculated to examine the potential relationships. Sensitivity and subgroup analyses were subsequently performed to determine the major causes of heterogeneity.

Heterogeneity was dramatically reduced after the removal of one study from the analysis (I2 = 37%, P = 0.19). The remaining studies involved 5-FU-based treatment. The presence of VEGF G-1154A and VEGF-634C/G was found to be correlated with patient response to 5-FU/CDDP-based treatment, whereas VEGF-2549I/D was correlated with response to 5-FU/oxaliplatin-based treatment, and VEGF-936C/T was associated with both 5-FU/CDDP- and 5-FU/oxaliplatin-based treatment response.

VEGF gene polymorphisms affect the response of esophageal squamous carcinoma patients receiving pharmaceutical therapy, especially 5-FU-based treatments.

One of the major limitations of cancer therapy is the emergence of drug resistance. This review amis to provide a focused analysis of the multifactorial mechanisms underlying therapy resistance,with an emphasis on actionable insights for developing novel therapeutic strategies. It concisely outlines key factors contributing to therapy resistance, including drug delivery barriers, cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), cancer heterogeneity, tumor microenvironment (TME), genetic mutations, and alterlations in gene expression. Additionally, we explore how tumors evade targeted therapies through pathway-specific mechanisms that restore disrupted signaling pathways. The review critically evaluates innovative strategies designed to sensitize resistant tumor cells, such as targeted protein dedgradation, antibody-drug conjugates, structure-based drug design, allosteric drugs, multitarget drugs, nanomedicine and others We also highlight the importance of understanding the pharmacological actions of these agents and their integration into treatment regimens. By synthesizing current knowledge and identifying gaps in our understanding, this review aims to guide future research and improve patient outcomes in cancer therapy.

Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, with delayed diagnosis often limiting effective treatment options. This study introduces a novel, noninvasive radiomics-based approach using [18F] FDG PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) to predict vascular endothelial growth factor (VEGF) status and survival in patients with GC. The ability to noninvasively assess these parameters can significantly influence therapeutic decisions and outcomes.

We conducted a retrospective study involving patients diagnosed with GC, stratified into training, validation, and test groups. Each patient underwent a [18F] FDG PET/CT scan, and radiomic features were extracted using dedicated software. A Radiomics Score (RS) was calculated, serving as a predictor for VEGF status. Statistical analyses included logistic regression and Cox proportional hazards models to evaluate the predictive power of RS on survival outcomes.

The developed radiomics model demonstrated high predictive accuracy, with the RS formula achieving an area under the receiver operating characteristic curve of 0.861 in the training cohort and 0.857 in the validation cohort for predicting VEGF status. The model also identified RS as an independent prognostic factor for survival, where higher RS values correlated with poorer survival rates.

The findings underscore the potential of [18F] FDG PET/CT radiomics in transforming the management of GC by providing a noninvasive means to assess tumor aggressiveness and prognosis through VEGF status. This model could facilitate earlier and more tailored therapeutic interventions, potentially improving survival outcomes in a disease marked by typically late diagnosis and limited treatment success.

Apatinib, a commonly used tyrosine kinase inhibitor in cancer treatment, can cause adverse reactions such as hypertension. Hypertension, in turn, can increase the risk of certain cancers. The coexistence of these diseases makes the use of combination drugs more common in clinical practice, but the potential interactions and regulatory mechanisms in these drug combinations are poorly understood. We used the humanized CYP2D6 mouse model to predict the effect of apatinib on the pharmacokinetics and pharmacodynamics of metoprolol and investigated the interactional mechanism. The inhibitory effects and mechanisms of apatinib on metoprolol were investigated in vitro by using wild-type mouse liver microsomes (WT MLMs), humanized CYP2D6 mouse liver microsomes (hCYP2D6 MLMs), and human liver microsomes (HLMs). Molecular docking was utilized to explore the structural basis of the observed inhibitory mode. And in vivo interaction between apatinib and metoprolol was assessed by pharmacokinetics study using the humanized CYP2D6 mice. In vitro studies and molecular docking experiments indicated that apatinib competitively inhibited the metabolism of metoprolol. In vivo findings revealed that the administration of apatinib combined with metoprolol resulted in a significant increase in the AUC(0-t), AUC(0-∞) and Cmax of metoprolol; additionally, there was a reduction in the CLz/F and heart rate, indicating that apatinib strongly inhibited metoprolol metabolism. And the homologous CYP2D6 protein in WT mice was more sensitive to apatinib compared to the hCYP2D6 mice. Gender analysis revealed that metoprolol accumulation was more pronounced in male mice when combined with apatinib, indicating a higher susceptibility to cardiotoxicity in males.

Apatinib is a small molecule anti-angiogenesis targeted drug that has demonstrated significant efficacy as a late-line treatment in advanced gastric cancer in phase 3 clinical trials. This study amid to evaluate the correlation between dose exposure intensity and efficacy and safety of apatinib in the treatment of advanced gastric cancer.

We conducted an observational, retrospective cohort study of patients with advanced gastric cancer who received apatinib targeted therapy in Beijing Friendship Hospital affiliated to Capital Medical University between June 1, 2018, and June 30, 2021. Dose exposure intensity (DEI) was defined as the product of dose and continuous medication time. Patients were assigned to high-dose exposure intensity (HDEI) and low-dose exposure intensity (LDEI) cohorts. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and safety. The relationship between HDEI and LDEI and clinical outcomes was analyzed by using the Kaplan-Meier curve and χ2 test.

61 patients were enrolled and assigned into two retrospective cohorts. The median PFS (mPFS) were 6.50 months (95% confidence interval (CI) [4.80-9.20]) and 4.10 months (95% CI [3.70-5.20]), and the median OS (mOS) were 10.70 months (95% CI [9.20-18.50]) and 7.50 months (95% CI [6.80-9.30]) for the HDEI and LDEI cohorts, respectively. The mPFS were 5.85 months (95% CI [5.00-7.00]) and 4.60 months (95% CI [4.10-5.90]), and mOS were 9.60 months (95% CI [9.10-12.40]) and 7.60 months (95% CI [7.20-10.20]) the for the 250 mg cohort and 500 mg cohorts. The mPFS were 6.65 months (95% CI [5.90-9.20]) and 4.10 months (95% CI [3.90-5.20]), and the mOS were 11.20 months (95% CI [9.20-18.50]) and 7.60 months (95% CI [7.20-9.60])for the long medication time and short medication time cohorts, respectively. The most common TRAEs of any grade were hypertension, proteinuria, and neutrophil count decreased. The incidence of grade 3-4 adverse reactions in the 500 mg cohort was higher than the 250 mg cohort (P=0.0016).

The efficacy of apatinib in advanced gastric cancer was significantly positively correlated with dose exposure intensity, and HDEI can prolong PFS and OS. Early application of low-dose apatinib (250 mg/d) can improve patients' tolerability, and the adverse reactions are controllable.

Treatment options for refractory advanced gastric and esophagogastric junction cancer (AGOC) are limited. Regorafenib, an oral multikinase inhibitor, prolonged progression-free survival (PFS) versus placebo in the INTEGRATE I phase II trial. INTEGRATE IIa was designed to examine whether regorafenib improved overall survival (OS).

A double-blind placebo-controlled phase III trial compared regorafenib and best supportive care (BSC) versus placebo and BSC for participants with confirmed evaluable metastatic/advanced AGOC who failed ≥two prior therapies on a 2:1 random assignment, stratified by tumor location, geographic region (Asia v rest of world), and prior vascular endothelial growth factor inhibitors. The primary end point was OS. Treatment efficacy on OS was first tested in the pooled INTEGRATE I + INTEGRATE IIa cohort and, if significant, then in the INTEGRATE IIa cohort. Secondary end points were PFS, objective response rate, safety, and quality of life (QoL).

INTEGRATE IIa enrolled 251 participants: 157 from Asia and 94 from rest of world and 169 received regorafenib and 82 received placebo. No significant heterogeneity was observed between INTEGRATE I and INTEGRATE IIa studies on OS. Pooled OS analysis hazard ratio (HR) was 0.70 (95% CI, 0.56 to 0.87; P = .001; 361 events). INTEGRATE IIa alone OS HR was 0.68 (95% CI, 0.52 to 0.90; P = .006; 238 events), the median OS was 4.5 months versus 4.0 months, and 12-month survival rates were 19% and 6%, for regorafenib versus placebo, respectively. After a preplanned adjustment for multiplicity, there were no statistically significant differences across regions or other prespecified subgroups. Regorafenib improved PFS (HR, 0.53 [95% CI, 0.40 to 0.70]; P < .0001) and delayed deterioration in global QoL (HR, 0.68 [95% CI, 0.52 to 0.89]; P = .0043). The toxicity profile was consistent with that of previous reports.

Regorafenib improves survival compared with placebo in refractory AGOC.

Thymic carcinoma (TC) is a rare form of highly invasive tumors. Currently, the standard first-line therapy involves paclitaxel plus carboplatin treatment, while the recommended regimen for second-line therapy remains uncertain. The purpose of this study is to explore the second-line mode of TC patients.

We evaluated the outcome of subjects with advanced TC between 2009 and 2023 in three medical centers, retrospectively. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Kaplan-Meier was used for calculating Progression-free survival (PFS) and overall survival (OS). The factors affecting survival in the real world were evaluated by Cox analysis.

Totally 136 patients were included in this study, the median PFS (mPFS) for all subjects was 5.97 months, and the median OS (mOS) was 25.03 months. According to patient's treatment modes, they are divided into monotherapy (n = 95) and combination therapy (n = 41), PFS manifested the difference between two groups (5.17 vs. 9.00 months, P = 0.043). OS also indicated a significant distinction (22.50 vs. 38.00 months, P = 0.017). Furthermore, there was a significant difference in PFS between patients using immunotherapy combined with chemotherapy and those with antivascular therapy (8.57 vs. 13.10 months, P = 0.047).

In the second-line therapy for advanced TC, the efficacy of combination therapy was better than monotherapy, especially for immunotherapy combined with antivascular therapy.

With relatively few direct comparisons among treatment options for previously treated advanced gastric cancer or gastroesophageal junction (GEJ) cancer, network meta-analysis (NMA) may inform evidence-based decision-making. Ramucirumab plus paclitaxel (RAM + PTX) is a preferred regimen in guideline recommendations. NMA of key outcomes may further characterize the relative clinical value of RAM + PTX.

A systematic literature review of randomized controlled trials of adult patients with previously treated advanced gastric/GEJ cancer informed a NMA which compared overall survival, progression-free survival, and discontinuations due to adverse events. Comparisons were reported relative to placebo/best supportive care (BSC) when possible, otherwise relative to RAM + PTX.

The base-case NMA focused on second-line treatment only, from 19 of 28 studies identified. For overall survival, seven of 16 regimens were favorable relative to placebo/BSC, with RAM + PTX as the most favorable. For progression-free survival, five of 14 regimens were unfavorable relative to RAM + PTX. For discontinuations due to adverse events, two of 13 regimens were similar to placebo/BSC: ramucirumab monotherapy and fluorouracil; relative to RAM-PTX, all regimens were similar except ramucirumab monotherapy which was favorable and irinotecan + cisplatin which was unfavorable.

This NMA of trials of previously treated gastric/GEJ cancer suggests that RAM + PTX has one of the more favorable clinical profiles.

Gastric cancer (GC) poses a significant global health challenge, ranking fifth in incidence and third in mortality among all malignancies worldwide. Its insidious onset, aggressive growth, proclivity for metastasis, and limited treatment options have contributed to its high fatality rate. Traditional approaches for GC treatment primarily involve surgery and chemotherapy. However, there is growing interest in targeted therapies and immunotherapies. This comprehensive review highlights recent advancements in GC targeted therapy and immunotherapy. It delves into the mechanisms of various strategies, underscoring their potential in GC treatment. Additionally, the review evaluates the efficacy and safety of relevant clinical trials. Despite the benefits observed in numerous advanced GC patients with targeted therapies and immunotherapies, challenges persist. We discuss pertinent strategies to overcome these challenges, thereby providing a solid foundation for enhancing the clinical effectiveness of targeted therapies and immunotherapies.

Data on long-term cancer survivors treated with apatinib are lacking. This study aimed to describe the characteristics of long-term cancer survivors after apatinib-based therapy, and to know about their satisfaction degree with apatinib and severity of depression and insomnia.

Patients with solid tumors who had received apatinib-based therapy for at least 5 years were invited to complete an online questionnaire. Characteristics of patients and treatment, knowledge of apatinib, satisfaction degree, and severity of depression and insomnia assessed by Patient Health Questionnaire-9 and Insomnia Severity Index were collected.

Between December 8, 2023 and March 1, 2024, a total of 436 patients completed the online questionnaire. Most patients were satisfied with the efficacy (96.6%) and safety (93.1%) of apatinib, were willing to continue apatinib treatment (99.5%), and would recommend apatinib to other patients (93.3%). Continuous apatinib treatment resulted in significant negative impact on daily life, work, or study in only two (0.5%) patients. Almost all patients currently had no or mild depression (97.0%) and insomnia (97.9%) problems. The most common patient-reported adverse events were hand-foot syndrome (21.3%) and hypertension (18.3%).

Our survey showed a high satisfaction degree with apatinib in long-term cancer survivors. Long-term apatinib treatment resulted in almost no negative impact on patient's quality of life.

With one of the highest mortality rates of all malignancies, the 5-year survival rate for esophageal cancer is under 20%. Depending on the stage and extent of the disease, the current standard of care treatment paradigm includes chemotherapy or chemoradiotherapy followed by surgical esophagogastrectomy, with consideration for adjuvant immunotherapy for residual disease. This regimen has high morbidity, due to anatomic changes inherent in surgery, the acuity of surgical complications, and off-target effects of systemic chemotherapy and immunotherapy. We begin with a review of current treatments, then discuss new and emerging targets for therapies and advanced drug delivery systems. Recent and ongoing preclinical and early clinical studies are evaluating traditional tumor targets (e.g., human epidermal growth factor receptor 2), as well as promising new targets such as Yes-associated protein 1 or mammalian target of rapamycin to develop new treatments for this disease. Due the function and location of the esophagus, opportunities also exist to pair these treatments with a drug delivery strategy to increase tumor targeting, bioavailability, and intratumor concentrations, with the two most common delivery platforms being stents and nanoparticles. Finally, early results with antibody drug conjugates and chimeric antigenic receptor T cells show promise as upcoming therapies. This review discusses these innovations in therapeutics and drug delivery in the context of their successes and failures, with the goal of identifying those solutions that demonstrate the most promise to shift the paradigm in treating this deadly disease.

Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers.

We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR).

Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response.

Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation.

Chinese Clinical Trial Registry, ChiCTR1900023277.

EGFR-tyrosine kinase inhibitor (TKI) is used to treat recurrent and metastatic nasopharyngeal carcinoma (rmNPC). This meta-analysis aims to study the efficacy and safety of EGFR-TKI in treating patients with rmNPC.

We conducted a systematic search of PubMed, Embase, and Web of Science up to November 2023, and included literature that met the criteria. We extracted objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse reaction-related events and performed meta-analysis using Stata 14.0.

A total of nine articles were included. The summary results showed that the ORR for patients treated with EGFR-TKI for rmNPC was 38% (95% CI = 27%-49%), the DCR was 71% (95% CI = 61%-80%), the mPFS was 6.29 months (95% CI = 5.22-7.35), and the mOS was 15.94 months (95% CI = 14.68-17.20). The most common grade 3-4 adverse reaction events in these patients were mucositis, nasopharyngeal necrosis, and oral ulceration. We found an incidence rate of 49% (95% CI = 38%-61%) for grade 3-4 adverse events (AEs). The anti-PD1 combined with TKI treatment method is more effective than the EGFR-TKI alone for treating rmNPC.

The study shows that EGFR-TKI has good efficacy in treating rmNPC but does not translate into survival benefits and owns a high incidence of grade 3-4 AEs. More RCT trials are needed in the future to verify the efficacy of anti-PD1 combined with TKI treatment method.

Brain metastases (BM) are very rare in gastric adenocarcinoma (GaC), and patients with BMs have a higher mortality rate due to stronger tumor aggressiveness. However, its pathogenesis remains unclear. Genetic testing revealed cellular-mesenchymal epithelial transition factor receptor (MET) amplification. Therefore, treatment with savolitinib, a small molecule inhibitor of c-Met, was selected.

A 66-year-old woman was diagnosed with advanced GaC 6 months prior to presentation due to back pain. Cerebellar and meningeal metastases were observed during candonilimab combined with oxaliplatin and capecitabine therapy. The patient experienced frequent generalized seizures and persistent drowsiness in the emergency department. Genetic testing of cerebrospinal fluid and peripheral blood revealed increased MET amplification. After discussing treatment options with the patient, savolitinib tablets were administered. After a month of treatment, the intracranial lesions shrank considerably.

BM is very rare in advanced GaC, especially in meningeal cancer, that is characterized by rapid disease deterioration. There are very few effective treatment options available; however, technological breakthroughs in genomics have provided a basis for personalized treatment. Furthermore, MET amplification may be a key driver of BM in gastric cancer; however, this conclusion requires further investigation.

Immunotherapy or apatinib alone has been used as third-line adjuvant therapy for advanced or metastatic gastric/gastroesophageal junction (G/GEJ) tumors, but the efficacy of combining them with each other for the treatment of patients with advanced or metastatic G/GEJ is unknown; therefore, we further evaluated the efficacy and safety of immunotherapy combined with apatinib in patients with advanced or metastatic G/GEJ.

The main search was conducted on published databases: Embase, Cochrane library, PubMed.The search was conducted from the establishment of the database to December 2023.Clinical trials with patients with advanced or metastatic G/GEJ and immunotherapy combined with apatinib as the study variable were collected. Review Manager 5.4 software as well as stata 15.0 software were used for meta-analysis.

A total of 651 patients from 19 articles were included in this meta-analysis. In the included studies, immunotherapy combined with apatinib had a complete response (CR) of 0.03 (95% CI: 0.00 -0.06), partial response (PR) of 0.34 (95% CI: 0.19-0.49), stable disease (SD) of 0.43 (95% CI: 0.32-0.55), objective response rate (ORR) was 0.36 (95% CI: 0.23-0.48), disease control rate (DCR) was 0.80 (95% CI: 0.74-0.86), and median progression-free survival (PFS) was 4.29 (95% CI: 4.05-4.52), median Overall survival (OS) was 8.79 (95% CI: 7.92-9.66), and the incidence of grade ≥ 3 TRAEs was 0.34 (95% CI: 0:19-0.49). PR, ORR, DCR, median PFS and median OS were significantly higher in the immunotherapy and apatinib combination chemotherapy group (IAC) than in the immunotherapy combination apatinib group (IA). And the difference was not significant in the incidence of SD and grade ≥ 3 TRAEs.

This meta-analysis shows that immunotherapy combined with apatinib is safe and effective in the treatment of advanced or metastatic G/GEJ, where IAC can be a recommended adjuvant treatment option for patients with advanced or metastatic G/GEJ. However, more large multicenter randomized studies are urgently needed to reveal the long-term outcomes of immunotherapy combined with apatinib treatment.

The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy.

Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores.

Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes.

Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup.

This study was designed to investigate the efficacy and safety of apatinib monotherapy in the treatment of elderly patients with advanced colorectal cancer (CRC) who have progressed on the standard regimens.

The data of 106 elderly patients with advanced CRC who have progressed on standard treatment were analyzed. The primary endpoint of this study was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and overall survival (OS). The safety outcomes were assessed by the proportion and severity of adverse events.

Efficacy was assessed using the best overall response of patients during treatment with apatinib, including 0 patients with complete response, 9 patients with partial response, 68 patients with stable disease, and 29 patients with progressive disease. ORR and DCR were 8.5 and 72.6%, respectively. The median PFS of 106 patients was 3.6 months, and the median OS was 10.1 months. The most frequent adverse reactions of elderly patients with advanced CRC receiving apatinib treatment were hypertension (59.4%) and hand-foot syndrome (HFS) (48.1%). The median PFS of patients with and without hypertension was 5.0 and 3.0 months, respectively ( P = 0.008). The median PFS of patients with and without HFS was 5.4 and 3.0 months, respectively ( P = 0.013).

The clinical benefit of apatinib monotherapy was observed in elderly patients with advanced CRC who have progressed on the standard regimens. The adverse reactions of hypertension and HFS were positively related to treatment efficacy.

The combined treatment of transcatheter arterial chemoembolization (TACE) and apatinib had beneficial effects on the survival of patients with advanced hepatocellular carcinoma (HCC), but the efficacy of this regimen is still controversial and needs further investigation.

The clinical records of advanced HCC patients between May 2015 and December 2016 were collected from our hospital. They were categorized into the TACE monotherapy group and the combination of TACE and apatinib group. After propensity score matching (PSM) analysis, the disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and occurrence of adverse events were compared between the two treatments.

There were 115 HCC patients included in the study. Among them, 53 received TACE monotherapy and 62 were treated with TACE plus apatinib. After PSM analysis, 50 pairs of patients were compared. The DCR of the TACE group was significantly lower than that of the combination of TACE and apatinib group (35 [70%] versus 45 [90%], P < 0.05). The ORR of the TACE group was also significantly lower than that of the combination of TACE and apatinib group (22 [44%] versus 34 [68%], P < 0.05). Patients who received the combined treatment of TACE and apatinib had longer PFS compared with those in the TACE monotherapy group ( P < 0.001). Moreover, hypertension, hand-foot syndrome, and albuminuria were more common in the combination of TACE and apatinib group ( P < 0.05), although all adverse events were well tolerated.

The combined treatment of TACE and apatinib showed beneficial effects on tumor response, survival outcomes, and tolerance to treatment, which may be used as a routine regimen for advanced HCC patients.

Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1-14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8-89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).

Rivoceranib is an oral, selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. ANGEL (NCT03042611) was a global, randomized, double-blinded, placebo-controlled, phase 3 study evaluating rivoceranib as 3rd-line or ≥4th-line therapy in patients with advanced/metastatic gastric or gastroesophageal junction (GEJ) cancer.

Patients had failed ≥2 lines of chemotherapy and were randomized 2:1 to rivoceranib 700 mg once daily or placebo with best supportive care.

overall survival (OS) in the intention-to-treat population. Secondary endpoints: progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) by blinded independent central review (BICR).

In total, 460 patients (rivoceranib n = 308, placebo n = 152) were enrolled. OS was not statistically different for rivoceranib versus placebo (median 5.78 vs. 5.13 months; hazard ratio [HR] 0.93, 95% CI 0.74-1.15; p = 0.4724). PFS by BICR (median 2.83 vs. 1.77 months; HR 0.58, 95% CI 0.47-0.71; p < 0.0001), ORR (6.5% vs. 1.3%; p = 0.0119), and DCR (40.3 vs. 13.2%; p < 0.0001) were improved with rivoceranib versus placebo. In patients receiving ≥4th-line therapy, OS (median 6.34 vs. 4.73 months; p = 0.0192) and PFS by BICR (median 3.52 vs. 1.71 months; p < 0.0001) were improved with rivoceranib versus placebo. The most common grade ≥ 3 treatment-emergent adverse events with rivoceranib were hypertension (17.9%), anemia (10.4%), aspartate aminotransferase increased (9.4%), asthenia (8.5%), and proteinuria (7.5%).

This study did not meet its primary OS endpoint. Compared to placebo, rivoceranib improved PFS, ORR, and DCR. Rivoceranib also improved OS in a prespecified patient subgroup receiving ≥4th-line therapy.

This review critically examines the latest approaches in treating advanced gastroesophageal malignancies. It emphasizes the significance of angiogenesis as a therapeutic target and discusses the potential synergy of combining angiogenesis inhibitors with immune checkpoint inhibitors (ICIs) to enhance treatment efficacy.

Emerging evidence from clinical trials, such as the INTEGRATE IIa trial with regorafenib and studies involving apatinib and sunitinib, underscores the efficacy of targeting the VEGFR pathway. These studies indicate substantial benefits in progression-free survival (PFS) and overall survival (OS) in patients with advanced stages of the disease who have limited treatment options. Additionally, the recent introduction of combination therapies involving ICIs has shown an increased response rate, suggesting a promising direction for future treatment protocols. The landscape of treatment for gastroesophageal malignancies is rapidly evolving. Research is now pivoting from conventional chemotherapy to a more nuanced approach that includes targeted therapy and immunotherapy.

This study aimed to evaluate the efficacy and safety of the combination of sintilimab and apatinib for the treatment of patients with advanced or metastatic gastric cancer (GC) and gastroesophageal junction (GEJ) cancer. This retrospective study analyzed data from 34 patients who had advanced or metastatic GC/GEJ cancer and received the combination therapy of sintilimab and apatinib as a third-line or above treatment. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Among the 34 patients, none achieved a complete response (CR), 3 patients (8.8%) achieved a partial response, 23 patients (67.6%) had stable disease, and 8 patients (23.5%) experienced progressive disease. The ORR and DCR were 8.8% and 76.5%, respectively. The median PFS was 6.0 months (95% CI: 3.6-8.4), and the median OS was 11.6 months (95% CI: 8.1-15.1). Subgroup analysis revealed significant differences in OS between patients with high and low Eastern Cooperative Oncology Group Performance Status scores and between patients with and without a history of gastrectomy. Common adverse events (AEs) during treatment included fatigue (52.9%), anemia (47.1%), leukopenia (26.5%), hypothyroidism (23.5%), nausea and vomiting (20.6%), neutropenia (20.6%), and thrombocytopenia (17.6%), most of which were grade 1 and 2 AEs. No deaths occurred due to AEs. These findings indicate that the combination of sintilimab and apatinib has a favorable therapeutic effect in patients with advanced GC. Moreover, the AEs associated with this therapy are generally manageable.

Gastric cancer (GC) stands as a prevalent and deadly global malignancy. Despite its role as a preoperative neoadjuvant therapy, Apatinib's effectiveness is curtailed among GC patients exhibiting elevated YY1 expression. YY1's connection to adverse prognosis, drug resistance, and GC metastasis is established, yet the precise underlying mechanisms remain elusive. This study aims to unravel potential pathogenic pathways attributed to YY1.

Utilizing bioinformatics analysis, we conducted differentially expressed genes, functional annotation, and pathway enrichment analyses, and further validation through cellular and animal experiments.

Higher YY1 expression correlated with diminished postoperative progression-free survival (PFS) and disease-specific survival (DSS) rates in TCGA analysis, identifying YY1 as an independent DSS indicator in gastric cancer (GC) patients. Notably, YY1 exhibited significantly elevated expression in tumor tissues compared to adjacent normal tissues. Bioinformatics analysis revealed noteworthy differentially expressed genes (DEGs), transcriptional targets, factors, and co-expressed genes associated with YY1. LASSO Cox analysis unveiled Transferrin as a prospective pivotal protein regulated by YY1, with heightened expression linked to adverse DSS and PFS outcomes. YY1's role in governing the p53 signaling pathway and ferroptosis in GC cells was further elucidated. Moreover, YY1 overexpression dampened immune cell infiltration within GC tumors. Additionally, YY1 overexpression hindered GC cell ferroptosis and mediated Apatinib resistance via the p53 pathway. Remarkably, IFN-a demonstrated efficacy in reversing Apatinib resistance and immune suppression in GC tissues.

Our findings underscore the pivotal role of YY1 in driving GC progression and influencing prognosis, thus pinpointing it as a promising therapeutic target to enhance patient outcomes.

Gastrointestinal (GI) cancers encompass a group of malignancies affecting the digestive system, including the stomach, esophagus, liver, colon, rectum and pancreas. These cancers represent a significant global health burden, necessitating effective treatment strategies. Small-molecule drugs have emerged as crucial therapeutic options in the fight against GI cancers due to their oral bioavailability, targeted mechanisms of action, and well-established safety profiles. The review then elucidates the clinical applications and synthetic methods of clinically approved small-molecule drugs for the treatment of GI cancer, shedding light on their mechanisms of action and their potential in mitigating GI cancer progression. The review also discusses future prospects and the evolving landscape of small-molecule drug development in GI oncology, highlighting the potential for personalized medicine. In summary, this review provides valuable insights into cutting-edge strategies for harnessing clinically approved small-molecule drugs to combat GI cancer effectively.

The outcome of systemic therapy (ST) for unresectable and metastatic intrahepatic cholangiocarcinoma (iCCA) is poor. This study aims to further evaluate the efficacy and safety of locoregional therapy combined with systemic therapy (LRT + ST) compared with only ST in unresectable and metastatic iCCA by performing a systematic literature review and meta-analysis.

A comprehensive search was performed in PubMed, Web of Science, EMBASE, and the Cochrane Library up to November 3, 2022. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs).

Ten retrospective cohort studies with 3,791 unresectable or metastatic iCCA patients were enrolled in this study, including 1,120 who received ablation, arterially directed therapy (ADT), or external beam radiation therapy (EBRT) combined with ST. The meta-analysis showed that the LRT + ST group had a better OS (HR = 0.51; 95% CI =0.41-0.64; p value < 0.001), PFS (HR = 0.40, 95% CI = 0.22-0.71, p value = 0.002) and ORR (RR = 1.68; 95% CI = 1.17-2.42; p value = 0.005). Subgroup analysis showed that both ST combined with ADT (HR = 0.42, 95% CI = 0.31-0.56, p value < 0.001) and EBRT (HR = 0.67, 95% CI = 0.63-0.72, p value < 0.001) could improve OS. Neutropenia, thrombocytopenia, anemia, anorexia, and vomiting did not show significant differences between the groups (p value > 0.05).

Compared with only ST, LRT + ST improved survival outcomes for unresectable and metastatic iCCA patients without increasing severe AEs, which can further provide a basis for guidelines.

Although second-line treatments improve survival compared to best supportive care in patients with advanced gastric cancer with disease progression on first-line therapy, prognosis remains poor. A systematic review and meta-analysis were conducted to quantify the efficacy of second-or-later line systemic therapies in this target population.

A systematic literature review (January 1, 2000 to July 6, 2021) of Embase, MEDLINE, and CENTRAL with additional searches of 2019-2021 annual ASCO and ESMO conferences was conducted to identify studies in the target population. A random-effects meta-analysis was performed among studies involving chemotherapies and targeted therapies relevant in treatment guidelines and HTA activities. Outcomes of interest were objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) presented as Kaplan-Meier data. Randomized controlled trials reporting any of the outcomes of interest were included. For OS and PFS, individual patient-level data were reconstructed from published Kaplan-Meier curves.

Forty-four trials were eligible for the analysis. Pooled ORR (42 trials; 77 treatment arms; 7256 participants) was 15.0% (95% confidence interval (CI) 12.7-17.5%). Median OS from the pooled analysis (34 trials; 64 treatment arms; 60,350 person-months) was 7.9 months (95% CI 7.4-8.5). Median PFS from the pooled analysis (32 trials; 61 treatment arms; 28,860 person-months) was 3.5 months (95% CI 3.2-3.7).

Our study confirms poor prognosis among patients with advanced gastric cancer, following disease progression on first-line therapy. Despite the approved, recommended, and experimental systemic treatments available, there is still an unmet need for novel interventions for this indication.

Lymphocyte-monocyte ratio (LMR) has previously been used as a prognostic predictor in various solid tumors. This research aims in comparing the prognostic predictive Please check and conability of several inflammatory parameters and clinical parameters to validate further the excellent prognostic value of LMR in patients with gastric cancer treated with apatinib.

Monitor inflammatory, nutritional parameters and tumor markers. Cutoff values of the parameters concerned were identified with the X-tile program. Subgroup analysis was made via Kaplan-Meier curves, and univariate and multivariate Cox regression analyses were used to find independent prognostic factors. The nomogram of logistic regression models was constructed according to the results.

A total of 192 patients (115 divided into training group and 77 into validation group) who received the second- or later-line regimen of apatinib were retrospectively analyzed. The optimal cutoff value for LMR was 1.33. Patients with high LMR (LMR-H) were significantly longer than those with low LMR (LMR-L) in progression-free survival (median 121.0 days vs. median 44.5 days, P < 0.001). The predictive value of LMR was generally uniform across subgroups. Meanwhile, LMR and CA19-9 were the only hematological parameters with significant prognostic value in multivariate analysis. The area under the LMR curve (0.60) was greatest for all inflammatory indices. Adding LMR to the base model significantly enhanced the predictive power of the 6-month probability of disease progression (PD). The LMR-based nomogram showed good predictive power and discrimination in external validation.

LMR is a simple but effective predictor of prognosis for patients treated with apatinib.

At present, there are several studies on low-dose apatinib combined with chemotherapy as a second-line treatment of advanced gastric cancer (AGC), but the conclusions are controversial. Therefore, this meta-analysis aimed to evaluate the efficacy and safety of low-dose apatinib combined with chemotherapy as a second-line treatment of AGC.

Nine databases were searched for records on apatinib combined with chemotherapy in treating AGC from inception to June 2022. The observation group received low-dose apatinib combined with chemotherapy, while the controls received chemotherapy alone or other non-placebo treatments. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. The relative risk (RR) and weighted mean difference (WMD) were used as effect sizes.

Eight studies involving 679 patients were included in this meta-analysis. The results of the meta-analysis showed that the observation group was superior to the controls in terms of ORR (RR = 1.38, 95% confidence interval [CI]: 1.05-1.81, p = 0.02), DCR (RR = 1.35, 95% CI: 1.20-1.53, p < 0.001), OS (WMD = 4.72, 95% CI: 0.71-8.72, p < 0.001), and PFS (WMD = 2.67, 95% CI: 1.7-3.63, p < 0.001). There were no significant differences between the two groups in adverse events of any grade except hypertension (RR = 2.82, 95% CI: 2.07-3.84, p < 0.001), hand-mouth syndrome (RR = 1.84, 95% CI: 1.84-2.48, p < 0.001), and proteinuria (RR = 3.63, 95% CI: 2.31-5.7, p < 0.001).

Low-dose apatinib combined with chemotherapy as a second-line therapy is more effective in improving the efficacy of AGC compared to chemotherapy alone. However, this option has the potential to increase the risk of hypertension, hand-mouth syndrome, and proteinuria.

Introduction: In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have decreased. However, it has been reported that cardiovascular disease has become the second leading cause of long-term morbidity and fatality among cancer survivors. Cardiotoxicity from anticancer drugs affects the heart's function and structure and can occur during any stage of the cancer treatments, which leads to the development of cardiovascular disease. Objectives: To investigate the association between anticancer drugs for non-small cell lung cancer (NSCLC) and cardiotoxicity as to whether: different classes of anticancer drugs demonstrate different cardiotoxicity potentials; different dosages of the same drug in initial treatment affect the degree of cardiotoxicity; and accumulated dosage and/or duration of treatments affect the degree of cardiotoxicity. Methods: This systematic review included studies involving patients over 18 years old with NSCLC and excluded studies in which patients' treatments involve radiotherapy only. Electronic databases and registers including Cochrane Library, National Cancer Institute (NCI) Database, PubMed, Scopus, Web of Science, ClinicalTrials.gov and the European Union Clinical Trials Register were systematically searched from the earliest available date up until November 2020. A full version protocol of this systematic review (CRD42020191760) had been published on PROSPERO. Results: A total of 1785 records were identified using specific search terms through the databases and registers; 74 eligible studies were included for data extraction. Based on data extracted from the included studies, anticancer drugs for NSCLC that are associated with cardiovascular events include bevacizumab, carboplatin, cisplatin, crizotinib, docetaxel, erlotinib, gemcitabine and paclitaxel. Hypertension was the most reported cardiotoxicity as 30 studies documented this cardiovascular adverse event. Other reported treatment-related cardiotoxicities include arrhythmias, atrial fibrillation, bradycardia, cardiac arrest, cardiac failure, coronary artery disease, heart failure, ischemia, left ventricular dysfunction, myocardial infarction, palpitations, and tachycardia. Conclusion: The findings of this systematic review have provided a better understanding of the possible association between cardiotoxicities and anticancer drugs for NSCLC. Whilst variation is observed across different drug classes, the lack of information available on cardiac monitoring can result in underestimation of this association. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191760, identifier PROSPERO CRD42020191760.

The incidence of gastric cancer is increasing year by year. Most gastric cancers are already in the advanced stage with poor prognosis when diagnosed, which means the current treatment is not satisfactory. Angiogenesis is an important link in the occurrence and development of tumors, and there are multiple anti-angiogenesis targeted therapies. To comprehensively evaluate the efficacy and safety of anti-angiogenic targeted drugs alone and in combination against gastric cancer, we systematically searched and sorted out relevant literature. In this review, we summarized the efficacy and safety of Ramucirumab, Bevacizumab, Apatinib, Fruquintinib, Sorafenib, Sunitinib, Pazopanib on gastric cancer when used alone or in combination based on prospective clinical trials reported in the literature, and sorted response biomarkers. We also summarized the challenges faced by anti-angiogenesis therapy for gastric cancer and available solutions. Finally, the characteristics of the current clinical research are summarized and suggestions and prospects are raised. This review will serve as a good reference for the clinical research of anti-angiogenic targeted drugs in the treatment of gastric cancer.

To identify, describe, and organize the available evidence regarding systemic oncological treatments compared to best supportive care (BSC) for advanced gastresophageal cancer.

We conducted a thorough search across MEDLINE (PubMed), EMbase (Ovid), The Cochrane Library, Epistemonikos, PROSPERO, and Clinicaltrials.gov. Our inclusion criteria encompassed systematic reviews, randomized controlled trials, quasi-experimental and observational studies involving patients with advanced esophageal or gastric cancer receiving chemotherapy, immunotherapy or biological/targeted therapy compared to BSC. The outcomes included survival, quality of life, functional status, toxicity, and quality of end-of-life care.

We included and mapped 72 studies, comprising SRs, experimental and observational designs, 12 on esophageal cancer, 51 on gastric cancer, and 10 both locations. Most compared schemes including chemotherapy (47 studies), but did not report therapeutic lines. Moreover, BSC as a control arm was poorly defined, including integral support and placebo. Data favor the use of systemic oncological treatments in survival outcomes and BSC in toxicity. Data for outcomes including quality of life, functional status, and quality of end-of-life care were limited. We found sundry evidence gaps specifically in assessing new treatments such as immunotherapy and important outcomes such as functional status, symptoms control, hospital admissions, and the quality of end-life care for all the treatments.

There are important evidence gaps regarding new for patients with advanced gastresophageal cancer and the effect of systemic oncological treatments on important patient-centered outcomes beyond survival. Future research should clearly describe the population included, specifying previous treatments and considering therapeutic, and consider all patient-centered outcomes. Otherwise, it will be complex to apply research results into practice.

Local combined systemic therapy has been an important method for the treatment of unresectable hepatocellular carcinoma (HCC).The purpose of this study was to compare the effectiveness and safety of transarterial chemoembolization (TACE) plus Sorafenib versus TACE plus Apatinib for treating patients with unresectable HCC.

The clinical data of patients with unresectable HCC who were treated with TACE plus Sorafenib or TACE plus Apatinib at 5 Chinese medical centers between January 2016 and December 2020 were retrospectively analyzed. Propensity score matching (PSM) was applied to reduce the bias from confounding factors.

A total of 380 patients were enrolled, of whom 129 cases were treated with TACE plus Sorafenib and 251 cases with TACE plus Apatinib. After the 1:1 PSM, 116 pairs of patients were involved in this study. The results showed that the PFS and OS in the TACE-Sorafenib group were significantly longer than those in the TACE-Apatinib group (PFS: 16.79 ± 6.45 vs. 14.76 ± 6.98 months, P = 0.049; OS: 20.66 ± 6.98 vs. 17.69 ± 6.72 months, P = 0.013). However, the ORR in the TACE-Apatinib group was markedly higher than that in the TACE-Sorafenib group (70.69% vs. 56.03%, P = 0.021). There were more patients with adverse events (AEs) in the TACE-Apatinib group than those in the TACE-Sorafenib group before dose adjustment (87 vs. 63, P = 0.001); however, the number of patients who suffered from AEs was not significantly different between the two groups after the dose adjustment (62 vs. 55, P = 0.148). No treatment-related death was found in the two groups. Subgroup analysis revealed that patients with unresectable HCC could better benefit from regular doses than reduced doses (Sorafenib, 22.59 vs. 18.02, P < 0.001; Apatinib, 19.75 vs. 16.86, P = 0.005).

TACE plus either Sorafenib or Apatinib could effectively treat patients with unresectable HCC, the safety of TACE plus Sorafenib was better. and the ORR of TACE plus Apatinib was higher.

Vascular endothelial growth factor receptor 2 (VEGFR2), a key regulator of tumor angiogenesis, is highly expressed across numerous tumor types and has been an attractive target for anti-cancer therapy. However, clinical application of available VEGFR2 inhibitors has been challenged by limited efficacy and a wide range of side effects, potentially due to inadequate selectivity for VEGFR2. Thus, development of potent VEGFR2 inhibitors with improved selectivity is needed. Rivoceranib is an orally administered tyrosine kinase inhibitor that potently and selectively targets VEGFR2. A comparative understanding of the potency and selectivity of rivoceranib and approved inhibitors of VEGFR2 is valuable to inform rationale for therapy selection in the clinic. Here, we performed biochemical analyses of the kinase activity of VEGFR2 and of a panel of 270 kinases to compare rivoceranib to 10 FDA-approved kinase inhibitors ("reference inhibitors") with known activity against VEGFR2. Rivoceranib demonstrated potency within the range of the reference inhibitors, with a VEGFR2 kinase inhibition IC₅₀ value of 16 nM. However, analysis of residual kinase activity of the panel of 270 kinases showed that rivoceranib displayed greater selectivity for VEGFR2 compared with the reference inhibitors. Differences in selectivity among compounds within the observed range of potency of VEGFR2 kinase inhibition are clinically relevant, as toxicities associated with available VEGFR2 inhibitors are thought to be partly due to their effects against kinases other than VEGFR2. Together, this comparative biochemical analysis highlights the potential for rivoceranib to address clinical limitations associated with off-target effects of currently available VEGFR2 inhibitors.

Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings.

Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan-Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method.

Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6-5.4%), and DCR was 35.8% (95% CI, 33.7-38.0%). The median PFS was 2.7 months (95% CI 2.2-2.8), and the median OS was 5.8 months (95% CI 5.4-6.1).

The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment.

This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.