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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 
 EUROPEAN JOURNAL OF CANCER, Vol.144 : 49-60, 2021-02 
Journal Title
Issue Date
Advanced gastric cancer ; Antiangiogenic agents ; Bayesian analysis ; Immunotherapy ; Network meta-analysis ; Systematic review ; Third-line treatments
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine (예방의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seul-gi(김슬기) ORCID logo https://orcid.org/0000-0003-1641-4059
Nam, Chung Mo(남정모) ORCID logo https://orcid.org/0000-0003-0985-0928
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
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