Although anthracycline-based triplets are one of the most widely used regimens for the treatment of advanced gastric cancer (AGC), the incremental benefit associated with the inclusion of anthracyclines in therapeutic combinations is unknown. The aim of this study is to evaluate the efficacy and tolerance of epirubicin triplets vs platinum-fluoropyrimidine doublets in a national AGC registry.
We recruited patients with AGC treated at 28 Spanish centers with polychemotherapy, without trastuzumab, from 2008 to 2016. The effect of anthracycline-based triplets was assessed by propensity score matching (PSM) and Cox proportional hazards (PH) regression.
1002 patients (doublets, n = 653, triplets with anthracyclines, n = 349) were included. In the multivariate Cox PH regression model, there was no significant increase in OS in favor of anthracycline-based triplets: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contains 325 pairs with similar baseline characteristics. There was also no increase of OS with this method: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), (stratified log-rank test, p = 0.226), for doublets without anthracyclines vs anthracycline-based triplets. Objective responses were higher with triplets: 32.9% vs. 24.0% (p = 0.014) without significant differences in PFS: HR 0.95 (CI 95%, 0.80-1.13), stratified log-rank test, p = 0.873. Triplets were associated with higher hematological toxicity, and increased toxicity-related admissions by 86%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision.
Anthracycline triplets increased the antitumor effect (objective responses) of the treatment. However, they were not associated with an incremental benefit in PFS or OS and instead had a higher toxicity.
Clinical trial identification
Legal entity responsible for the study
Paula Jimenez Fonseca
All authors have declared no conflicts of interest.