First-line triplet or doublet chemotherapy for advanced gastric cancer: Analysis of 970 patients from a community practice registry

There is no consensus as to the optimal first-line chemotherapy for patients with advanced gastric cancer (AGC) and up to 10 polychemotherapy schemes can be considered appropriate in this setting. This study aims to evaluate the efficacy and tolerance of triplets versus doublets by analyzing a national gastric cancer registry. The AGAMENON registry included patients with AGC treated with polychemotherapy without trastuzumab from 2008-2016. The effect of triplets vs. doublets was compared using three methods: Cox proportional hazards (PH) regression, Propensity Score Matching (PSM), and Coarsened Exact Matching (CEM). 970 patients from 28 centers were recruited. Triplets were associated with better survival, with a hazard ratio (HR) 0.84 (95% confidence interval (CI), 0.72-0.98), p= 0.035. After adjusting for confounding factors (Cox model) and after PSM, a significant increase in survival, 11.14 (95% CI, 9.60-12.68) vs. 9.60 months (95% CI, 8.44-10.75) was seen in favor of triplets; HR 0.77 (95% CI, 0.65-0.92), stratified log-rank test, p = 0.004. The trend was similar after CEM with a HR 0.76 (95% CI, 0.61-0.94), p = 0.015. Higher response rates were seen with triplets than doublets: 49.6% vs. 39.2%. In the binary logistic regression, the variables associated with the use of triplets were: not having a chronic cardiopathy; good performance status (ECOG 0-1); age; unresectable, locally advanced tumors (compared to metastatic disease); extrahepatic metastases; diffuse tumors; tumors with signet ring cells; high baseline CEA (≥10 ng/dL), and no prior perioperative chemotherapy. Triplets had more severe toxicity (grade 3-4) in comparison with doublets, particularly more febrile neutropenia (10.4% vs. 6.5%), hepatic toxicity (15.8% vs. 9.2%), and toxicity-related hospitalization (30.7% vs. 22.6%). Our study suggest that triplets might be associated with a discreet benefit in efficacy in AGC at the expense of a moderate increase in toxicity, although its observational design should be taken into account.