Early Weight Loss As A Prognostic Factor In Patients With Advanced Gastric Cancer: Analyses From Regard, Rainbow, And Rainfall Phase Iii Studies

Background Weight loss is common in advanced gastric and gastroesophageal junction adenocarcinoma (G/GEA); however, the prognostic implications of weight loss during the first cycle (C1) of chemotherapy remain poorly characterized. In this study, we investigated the impact of early weight loss during systemic treatment as a potential prognostic factor for overall survival (OS) in patients with advanced G/GEA.Materials and Methods We performed a post hoc analysis of three phase III studies of ramucirumab. Patients were categorized into two groups: weight loss of >= 3% and <3% based on weight change during C1 (3-4 weeks) of treatment. OS by weight groups was assessed for each study and as a pooled meta-analysis. The effect of C1 weight change on patient survival was evaluated using univariate and multivariate Cox models.Results A total of 1,464 patients with weight data at the end of C1 were analyzed: REGARD (n = 311), RAINBOW (n = 591), and RAINFALL (n = 562). For all three studies, there were fewer patients in the weight loss >= 3% than <3% group. OS was numerically shorter for patients with weight loss of >= 3% than for patients with weight loss of <3% during C1 irrespective of treatment arm. Similar treatment independent effects of early weight loss on OS were observed in the meta-analysis. Overall, early weight loss >= 3% was associated with shorter survival in patients receiving active drug as well as placebo/best supportive care.Conclusion This large post hoc analysis demonstrated that weight loss of >= 3% during C1 was a negative prognostic factor for OS in patients with advanced G/GEA.Implications for Practice This comprehensive analysis examining early weight loss during systemic treatment as a predictor of survival outcomes in patients with advanced gastric and gastroesophageal junction adenocarcinoma (G/GEA) includes a large sample size, reliable on-treatment data reported in well-conducted phase III clinical trials, and global representation of cancer patients with advanced G/GEA. Understanding the impact of on-treatment weight loss is clinically relevant and may represent an opportunity for targeted interventions.