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Efficacy and safety of targeting VEGFR drugs in treatment for advanced or metastatic gastric cancer: a systemic review and meta-analysis.

ABSTRACT: The value of targeting VEGFR (vascular endothelial growth factor receptor) drugs has demonstrated encouraging anti-cancer activity in advanced solid tumors within current clinical trials. This study aimed to serve as the first systemic review to assess their safety and efficacy according to biochemical characteristics of targeting VEGFR drugs in gastric cancer. We analyzed eight clinical trials on targeting VEGFR drugs in gastric cancer. Results showed that targeting VEGFR drugs significantly improved overall survival (OS) [Hazard Ratio (HR) 0.69, 95% confidence interval (CI) (0.55, 0.83), P < 0.001], progression free survival (PFS) [HR 0.50, 95% CI (0.34, 0.66), P < 0.001], disease control rate (DCR) [Odds Ratio (OR) 3.83, 95% CI (2.39, 6.15), P < 0.001] and significantly decreased the progressive disease rate(PDR)[OR 0.45, 95% CI (0.34, 0.59), P < 0.001], but not objective response rate (ORR) [OR 1.46, 95% CI (0.93, 2.29), P = 0.098]. Further subgroup revealed that VEGFR antibody (VEGFR-Ab) drugs were superior to VEGFR tyrosine kinase inhibitor (VEGFR-TKI) drugs in terms of the OS, PFS and PDR. To determine the toxic effect of targeting VEGFR drugs, the relative risk of adverse events (grade ? 3) of special interest(AESIs) were estimated. Most of these were predictable and manageable. Furthermore, less AESIs were observed in the VEGFR-Ab than the VEGFR-TKI drugs. In conclusion, VEGFR drugs were effective targeted therapy in advanced or metastatic gastric cancer, and its toxicity is within a controllable range. VEGFR-Ab drugs were more effective than VEGFR-TKI drugs in terms of the OS, PFS and PDR of gastric cancer patients with little toxicity.

SUBMITTER: Liu D

PROVIDER: S-EPMC5814287 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Efficacy and safety of targeting VEGFR drugs in treatment for advanced or metastatic gastric cancer: a systemic review and meta-analysis.

Liu Duanrui D Ma Xiaoli X Xiao Dongjie D Jia Yanfei Y Wang Yunshan Y

Oncotarget 20171219 8

The value of targeting VEGFR (vascular endothelial growth factor receptor) drugs has demonstrated encouraging anti-cancer activity in advanced solid tumors within current clinical trials. This study aimed to serve as the first systemic review to assess their safety and efficacy according to biochemical characteristics of targeting VEGFR drugs in gastric cancer. We analyzed eight clinical trials on targeting VEGFR drugs in gastric cancer. Results showed that targeting VEGFR drugs significantly im ...[more]

PMID: 29487720

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Project description:BackgroundOncolytic viruses (OVs) have shown prospects in advanced and metastatic cancer, and many clinical trials have been carried out. To compare OV therapies comprehensively and provide a categorized profile and ranking of efficacy and safety, a network meta-analysis was conducted.MethodsA total of 5948 studies were screened and 13 randomized controlled trials with 1939 patients, of whom 1106 patients received OV therapies, comparing four OVs (NTX-010, pexastimogene devacirepvec (Pexa-Vec), talimogene laherparepvec (T-VEC), and pelareorep) were included in a Bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcome measures: objective response rate (ORR) and grade ≥ 3 adverse events.ResultsCompared to systemic treatments alone, talimogene laherparepvec (T-VEC) (OR 7.00, 95% CI 1.90-26.00) and T-VEC plus systemic treatment (2.90, 0.80-11.00) showed better objective response rates (ORRs), whereas Pexa-Vec 1 * 109 pfu plus systemic treatment (0.91, 0.26-3.00) and pelareorep plus systemic treatment (1.10, 0.61-2.00) were found to be comparable. The grade ≥ 3 adverse event ranking of the treatments from worst to best was as follows: T-VEC (ranking probability 24%), Pexa-Vec 1 * 109 pfu plus systemic treatment (21%), Pexa-Vec 1 * 109 pfu (17%), T-VEC plus systemic treatment (13%), pelareorep plus systemic treatment (13%), systemic treatments (18%), Pexa-Vec 1 * 108 pfu (12%), and NTX-010 (20%).ConclusionsCompared with other oncolytic virus therapies for patients with advanced or metastatic cancer, T-VEC and T-VEC plus systemic treatment appear to provide the best ORR therapy in terms of monotherapy and combination respectively, but should be given with caution to grade ≥ 3 adverse events. Conversely, combining OVs with chemotherapy or target agents was demonstrated not to improve efficacy compared with chemotherapy or target agents alone. Combining OV therapies with immune-checkpoint inhibitors, instead of chemotherapy or target agents, tended to provide better ORRs without causing severe adverse events. This study will guide treatment choice and optimize future trial designs for investigations of advanced or metastatic cancer.

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Dataset Information

Efficacy and safety of targeting VEGFR drugs in treatment for advanced or metastatic gastric cancer: a systemic review and meta-analysis.

Publications

Efficacy and safety of targeting VEGFR drugs in treatment for advanced or metastatic gastric cancer: a systemic review and meta-analysis.

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