Early Weight Loss as a Prognostic Factor in Patients with Advanced Gastric Cancer: Analyses from REGARD, RAINBOW, and RAINFALL Phase III Studies

Abstract

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. Here, 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. Patients and Methods. We performed a post-hoc analysis of 3 phase III studies of ramucirumab. Patients were categorized into 2 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 3 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 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. The Oncologist ;9999:• • Implications for Practice: This comprehensive analysis examining early weight loss during systemic treatment as a predictor of survival outcomes in patients with advanced 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.

JPEN Journal Club 77. Adjusting for confounders

“…The feature of this report by Mansoor et al 1 that most caught my attention was related to the adjusted HRs. As we noted earlier, when the patients losing ≥3% weight were compared with those with less weight loss, there were striking differences, so any attempt to make direct comparisons between the two groups is limited by confounding.…”

“…2 of the report. 1 Adjusting is designed to account for such differences between the two populations. 9 It is typically based on demographic and clinical information that is collected during the study.…”

“…The American Society for Parenteral and Enteral Nutrition (ASPEN) Oncology Special Section held an online journal club on January 18, 2023. One of the two papers discussed during that meeting contained several reading points that I thought would be pertinent to Journal of Parenteral and Enteral Nutrition (JPEN) readers, 1 and I decided to discuss it in this issue of the JPEN Journal Club.…”

“…In an effort to reduce the amount of such confounding, adjusted HRs were calculated for each of the three trials; these data can be found in tab. 2 of the report 1 . Adjusting is designed to account for such differences between the two populations 9 .…”

Nutritional Risk Index as a Prognostic Factor Predicts the Clinical Outcomes in Patients With Stage III Gastric Cancer

“…Weight loss is common in advanced gastric cancer, and maintaining weight and adequate nutrition during systemic treatment (38). Moreover, the weight loss is usually caused by insufficient calorie intake as a result of tumor-related anorexia, malabsorption, hypermetabolism, and gastrointestinal obstruction (39).…”