Optimal duration of first-line chemotherapy for advanced gastric cancer: data from the AGAMENON registry.

Background: The optimal duration of first-line chemotherapy for patients with advanced gastric cancer is unknown. Diverse clinical trials have proposed different strategies including limited treatment, maintenance of some drugs, or treatment until progression.

Method: The sample comprises patients from the AGAMENON multicenter registry without progression after second evaluation of response. The objective was to explore the optimal duration of first-line chemotherapy. A frailty multi-state model was conducted.

Results: 415 patients were divided into three strata: discontinuation of platinum and maintenance with fluoropyrimidine until progression (30%, n = 123), complete treatment withdrawal prior to progression (52%, n = 216), and full treatment until progression (18%, n = 76). The hazard of tumor progression decreased by 19% per month with the full treatment regimen. However, we found no evidence that fluoropyrimidine maintenance (hazard ratio [HR] 1.07, confidence interval [CI] 95%, 0.69-1.65) worsened progression-free survival (PFS) with respect to treatment until progression. Predictive factors for PFS were ECOG performance status, ≥ 3 metastatic sites, prior tumor response, and bone metastases. Toxicity grade 3/4 was more common in those who continued the full treatment until progression vs fluoropyrimidine maintenance (16% vs 6%).

Conclusion: The longer duration of the full initial regimen exerted a protective effect on the patients of this registry. Platinum discontinuation followed by fluoropyrimidine maintenance yields comparable efficacy to treatment up to PD, with a lower rate of serious adverse events.