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Body Mass Index and Outcomes With Targeted Therapy, Immunotherapy, or Chemotherapy in Metastatic Melanoma

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Key Points

  • Obesity was associated with improved progression-free and overall survival in patients receiving targeted or immune therapy.
  • Survival benefit appeared to be restricted to obese men receiving targeted or immune therapy.

In a study reported in The Lancet Oncology, McQuade et al found that obesity was associated with improved outcomes in treatment of metastatic melanoma with targeted therapy or immunotherapy—but not chemotherapy—with a survival benefit appearing to be restricted to obese male patients.

Study Details

The retrospective study included 1,918 eligible patients from six cohorts treated with targeted therapy, immunotherapy, or chemotherapy between August 2006 and January 2016. These included two cohorts from trials of targeted therapy (dabrafenib [Tafinlar] plus trametinib [Mekinist] [n = 599] and vemurafenib [Zelboraf] plus cobimetinib [Cotellic]  [n = 240]); two cohorts treated with immunotherapy (one trial of ipilimumab [Yervoy] plus dacarbazine [n = 207] and a retrospective cohort treated with pembrolizumab [Keytruda], nivolumab [Opdivo], or atezolizumab [Tecentriq] [n = 331]); and two cohorts treated with chemotherapy (two trials of dacarbazine [n = 320 and n = 221]).

Patients were classified by body mass index (BMI) according to WHO definitions as underweight, normal, overweight, or obese. Underweight patients were excluded from analysis.

Overall, 694 patients (36%) were normal BMI, 711 (37%) were overweight, and 513 (27%) were obese.

Effect of Obesity

In pooled analysis, obesity vs normal BMI was associated with improved progression-free survival (average adjusted hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.66–0.90) and overall survival (HR = 0.74, 95% CI = 0.58–0.95). The benefit of obesity was restricted to patients treated with targeted therapy, with HRs of 0.72 (95% CI = 0.57–0.91) for progression-free survival and 0.60 (95% CI = 0.45–0.79) for overall survival, and to patients treated with immunotherapy, with respective HRs of 0.75 (95% CI = 0.56–1.00) and 0.64 (95% CI = 0.47–0.86). No significant associations were observed for chemotherapy, with respective HRs of 0.87 (95% CI = 0.65–1.17) and 1.03 (95% CI = 0.80–1.34). The association of BMI with overall survival for patients treated with targeted or immune therapies was significant among men (HR = 0.53, 95% CI = 0.40–0.70) but not among women (HR = 0.85, 95% CI = 0.61–1.18; P = .03 for interaction).

The investigators concluded, “Our results suggest that in patients with metastatic melanoma, obesity is associated with improved progression-free survival and overall survival compared with those outcomes in patients with normal BMI, and that this association is mainly seen in male patients treated with targeted or immune therapy. These results have implications for the design of future clinical trials for patients with metastatic melanoma, and the magnitude of the benefit found supports further investigation of the underlying mechanism of these associations.”

The study was supported by an ASCO/CCF Young Investigator Award, ASCO/CCF Career Development Award, MD Anderson Cancer Center (MDACC) Melanoma Moonshot Program, MDACC Melanoma SPORE, and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.

Jennifer L. McQuade, MD, of the Department of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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