Obesity Associated With Improved Outcomes in Some Metastatic Melanomas

A retrospective review found that obesity is associated with improved progression-free and overall survival in patients with metastatic melanoma. The benefit was largely restricted to male patients, and to those who received targeted therapy or immunotherapy.

“Obesity is an established risk factor for many malignancies, and is associated with worse outcomes in several cancers,” wrote study authors led by Jennifer L. McQuade, MD, of the University of Texas MD Anderson Cancer Center in Houston. “However, higher body mass index (BMI) has also been associated with improved outcomes in some cancers, a phenomenon dubbed the obesity paradox.”

Obesity’s role in melanoma outcomes has not been well studied before. In the new analysis, researchers analyzed a total of 2,046 metastatic melanoma patients in 6 independent cohorts; they included two cohorts of patients treated with targeted therapy (dabrafenib plus trametinib [599 patients] or vemurafenib plus cobimetinib [240 patients]), two cohorts treated with immunotherapy (ipilimumab plus dacarbazine [207 patients], or any of pembrolizumab, nivolumab, or atezolizumab [331 patients]), and two cohorts treated with chemotherapy (both treated with dacarbazine [320 and 221 patients]). The results were published in Lancet Oncology.

Of the full group of patients, 36% were normal weight, 37% were overweight, and 27% were obese. A pooled analysis of all the cohorts found that obesity, when compared with normal-weight patients, was associated with improved progression-free survival (PFS), with an adjusted hazard ratio (HR) of 0.77 (95% CI, 0.66–0.90). The same was true of overall survival (OS), with an adjusted HR of 0.74 (95% CI, 0.58–0.95).

That benefit, however, was restricted to certain subsets of patients. Obese patients who received targeted therapy fared better, with an HR for PFS of 0.72 (95% CI, 0.57–0.91) and for OS of 0.60 (95% CI, 0.45–0.79); the same was true for immunotherapy, with an HR for PFS of 0.75 (95% CI, 0.56–1.00) and for OS of 0.64 (95% CI, 0.47–0.86). There was no association among those treated with chemotherapy.

Also, obesity was associated with better outcomes in men, with an HR for OS of 0.53 (95% CI, 0.40–0.70), but there was no difference in women.

The authors wrote that these findings along with earlier research support the existence of an obesity paradox in melanoma, in which higher BMI is associated with increased disease risk but also a survival advantage in those with established or advanced disease. “Whether this inverse relationship is causal remains poorly understood,” they wrote. “These findings support the need to consider sex and BMI as stratification factors in trials, and to investigate the biological mechanisms underlying these unexpected results.”