Evaluating First-line Chemotherapy Regimens and Platinum Choices in HER2-Negative Metastatic Gastric Cancer: A Retrospective Analysis

Objective:The survival advantage of triplet versus doublet chemotherapy regimens and cisplatin versus oxaliplatin-based therapies for first-line treatment in human epidermal growth factor receptor 2 (HER2)-negative metastatic gastric cancer remains unclear.This study aimed to evaluate and compare the impact of these regimens on survival and safety. Material and Methods:This retrospective, single-centre analysis included 259 patients with HER2-negative metastatic gastric cancer treated between 2012 and 2021.Progression-free survival (PFS), overall survival (OS), and toxicity profiles were evaluated as primary outcomes.Multivariate Cox regression and subgroup analyses were conducted to identify significant prognostic factors and patient subsets benefitting most from specific treatments.Results: Median PFS and OS were not significantly different between triplet (n=188) and doublet (n=71) groups (PFS: 6.77 vs. 4.90 months; OS: 11.02 vs. 9.43 months; p>0.05 for both).Similarly, no significant differences were observed between oxaliplatin-based (n=59) and cisplatin-based (n=203) regimens (PFS: 6.15 vs. 6.33 months; OS: 11.8 vs. 10.5 months; p>0.05).Multivariate analysis demonstrated that oxaliplatin significantly reduced progression risk [hazard ratio (HR): 0.68, p=0.025] without a significant OS benefit.Triplet therapy had no significant impact on PFS or OS.Subgroup analyses showed OS benefits with triplet therapy in patients with poor differentiation/signet-ring cell histology (HR: 0.53, p=0.005), lymph node metastasis (HR: 0.67, p=0.045), and peritoneal metastasis (HR: 0.58, p=0.061).Oxaliplatin-based therapy particularly benefited patients, aged 65 years, with comorbidities, middle gastric tumours, or 2 metastatic sites. Conclusion:No general survival advantage was observed between the regimens, but specific subgroups appeared to benefit, warranting further investigation.