First-Line Treatment After Perioperative FLOT in Recurrent Gastric and Gastroesophageal Junction Cancer: A Turkish...

Background and Objectives: Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is the standard of care for resectable gastric and gastroesophageal junction adenocarcinoma; however, up to 50% of patients develop metastatic recurrence. These patients have prior exposure to platinum and taxane agents, and optimal first-line treatment in the metastatic setting remains undefined. This study aimed to characterize real-world treatment patterns and outcomes in patients progressing after perioperative FLOT, focusing on relapse timing and HER2 status. Materials and Methods: This retrospective, multicenter cohort study included 296 patients from 31 centers across Türkiye, stratified into early relapse (≤6 months, n = 114) and late relapse (>6 months, n = 182) groups. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards regression. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: Median PFS and OS for the entire cohort were 6 and 9 months, respectively. Early relapsers had significantly shorter median PFS (4 vs. 6 months, p = 0.029) and OS (8 vs. 12 months, p = 0.047); however, early relapse timing did not retain independent prognostic significance on multivariable analysis. No significant difference in PFS or OS was observed between cytotoxic chemotherapy regimens in either relapse group. HER2 positivity was the only independent predictor of improved PFS on multivariable Cox analysis (HR 0.48, 95% CI 0.29-0.81; p = 0.006). In the late relapse group, trastuzumab-based chemotherapy achieved a median PFS of 14 months and OS of 18 months, significantly superior to all cytotoxic regimens (PFS p = 0.007; OS p = 0.029). Conclusions: In patients progressing after perioperative FLOT, cytotoxic chemotherapy regimen selection did not demonstrate a statistically significant survival difference in this retrospective cohort, regardless of relapse timing. HER2 positivity is the dominant predictive biomarker, and trastuzumab-based therapy suggests a potential survival benefit that warrants prospective validation. Comprehensive biomarker profiling at metastatic diagnosis and prospective trials designed for this post-FLOT population are needed to establish evidence-based treatment standards.