McQuade JL, et al. - In this retrospective study, researchers assessed the link between body-mass index (BMI) and progression-free survival or overall survival in patients with metastatic melanoma who received targeted therapy, immunotherapy, or chemotherapy. Obesity vs normal BMI was found to be associated with improved progression-free survival and overall survival among patients with metastatic melanoma. Furthermore, this link was predominantly seen in male patients treated with targeted or immune therapy.

• Researchers performed this retrospective study to analyze independent cohorts of patients with metastatic melanoma assigned to treatment with targeted therapy, immunotherapy, or chemotherapy in randomised clinical trials and one retrospective study of patients treated with immunotherapy.
• Using the WHO definitions, patients were categorized by BMI as underweight, normal, overweight, or obese.
• Patients without BMI and underweight patients were excluded.
• The associations between BMI and progression-free survival or overall survival, stratified by treatment type and sex, were the primary outcomes.
• Multivariable analyses were performed in the independent cohorts.
• Researchers also combined adjusted hazard ratios in a mixed-effects meta-analysis to provide a precise estimate of the link between BMI and survival outcomes; meta-regression analyses were used to assess the heterogeneity.
• The predefined intention-to-treat population in the randomised controlled trials and all patients included in the retrospective study were analyzed.

• A total of 2046 patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy between Aug 8, 2006, and Jan 15, 2016 constituted the 6 cohorts.
• The analysis included a total of 1918 patients.
• The following were classified according to BMI as normal (694 [36%] patients), overweight (711 [37%]), or obese (513 [27%]): two cohorts containing patients from randomised controlled trials treated with targeted therapy (dabrafenib plus trametinib [n=599] and vemurafenib plus cobimetinib [n=240]), two cohorts containing patients treated with immunotherapy (one randomised controlled trial of ipilimumab plus dacarbazine [n=207] and a retrospective cohort treated with pembrolizumab, nivolumab, or atezolizumab [n=331]), and two cohorts containing patients treated with chemotherapy (two randomised controlled trials of dacarbazine [n=320 and n=221]).
• In the pooled analysis, researchers noted an association of obesity, compared with normal BMI, with improved survival in patients with metastatic melanoma (average adjusted hazard ratio [HR] 0·77 [95% CI 0·66–0·90] for progression-free survival and 0·74 [0·58–0·95] for overall survival).
• Findings demonstrated that the survival benefit associated with obesity was restricted to patients treated with targeted therapy (HR 0·72 [0·57–0·91] for progression-free survival and 0·60 [0·45–0·79] for overall survival) and immunotherapy (HR 0·75 [0·56–1·00] and 0·64 [0·47–0·86]).
• Researchers found no associations with chemotherapy (HR 0·87 [0·65–1·17, p_interaction=0·61] for progression-free survival and 1·03 [0·80–1·34, p_interaction=0·01] for overall survival).
• In addition, they noted that the association of BMI with overall survival for patients treated with targeted and immune therapies differed by sex, with inverse associations in men (HR 0·53 [0·40–0·70]), but no associations observed in women (HR 0·85 [0·61–1·18, p_interaction=0·03]).