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

Sejung Park, Chung Mo Nam, Seul Gi Kim, Ji Eun Mun, Sun Young Rha, Hyun Cheol Chung

Research output: Contribution to journalReview articlepeer-review

12 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)49-60
Number of pages12
JournalEuropean Journal of Cancer
Publication statusPublished - 2021 Feb

Bibliographical note

Funding Information:
This work was supported by a grant from the National R&D Program for Cancer Control , Ministry of Health and Welfare , Republic of Korea [grant number HA15C0005 ].

Publisher Copyright:
© 2020 Elsevier Ltd

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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