Comparative efficacy and tolerability of third-line treatments for advanced gastric cancer: A systematic review with Bayesian network meta-analysis. (February 2021)

• Record Type: Journal Article
• Authors: Park, Sejung; Nam, Chung Mo; Kim, Seul-Gi; Mun, Ji Eun; Rha, Sun Young; Chung, Hyun Cheol
• Is Part Of: European journal of cancer. Volume 144(2021)
• Page Start: 49
• Page End: 60
• Publication Date: 2021-02
• Subjects: Advanced gastric cancer -- Third-line treatments -- Systematic review -- Network meta-analysis -- Bayesian analysis -- Antiangiogenic agents -- Immunotherapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2020.10.030
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: The most effective agent for the third-line treatment of advanced/metastatic gastric cancer (AGC) has not yet been determined. The aim of this network meta-analysis is to compare the relative efficacy and tolerability of third-line treatments for AGC. Materials and methods: We conducted a comprehensive literature review of randomised clinical trials (RCTs) using four electronic databases. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs) were used as efficacy or tolerability outcomes. A Bayesian network meta-analysis with a random-effects model was used. Results: Seven RCTs involving 2601 patients and nine treatments were included. The results suggested that 1 mg/kg nivolumab (nivolumab1) + 3 mg/kg ipilimumab (ipilimumab3) (hazard ratio [HR] 0.59, 95% credible interval [Crl] 0.38–0.91) was the most effective treatment, followed by nivolumab (HR 0.63, 95% Crl 0.50–0.79), for prolonging OS. Regorafenib (HR 0.40, 95% Crl 0.28–0.58) was most likely to improve PFS, followed by apatinib (HR 0.45, 95% Crl 0.33–0.60). Nivolumab1 + ipilimumab3 and nivolumab were better at improving ORR, whereas nivolumab1 + ipilimumab3 had the highest toxicity based on the AEs. For benefit-risk ratio, nivolumab, apatinib or regorafenib appeared to be the best options. Chemotherapy or two different dose combinations of nivolumab and ipilimumab were ranked as the next options because of poor tolerability, despite good efficacy. Conclusion: Immunotherapy (nivolumab) or antiangiogenic agents (regorafenib and apatinib) are associated with benefits for benefit-risk ratio as third-line monotherapy. This study might serve as a guideline to aid in the selection of third-line treatments for AGC. Highlights: The most effective third-line treatment of advanced gastric cancer is still unresolved. The aim was to compare the efficacy and tolerability of third-line treatments. Systematic review and network meta-analysis were performed including nine treatments. Nivolumab1 plus ipilimumab3 was the most preferable treatment for overall survival. Regorafenib was the most effective treatment for improving progression free survival. The findings showed a beneficial effect of immunotherapy and antiangiogenic agents.