'Obesity Paradox' Offers Puzzling Survival Advantage in Men with Metastatic Melanoma

While obesity is a known risk factor for more than a dozen types of cancer — and poised to take over smoking as the leading preventable cause for the disease – it may actually play a beneficial role in men with metastatic melanoma, according to a recent study published in Lancet Oncology.

After examining almost 2,000 patients from six independent cohorts, researchers noticed what they called the “Obesity Paradox.” Men with metastatic melanoma being treated with targeted or immunotherapies who were obese — meaning their body mass index (BMI) was over 30 – had nearly double the overall survival (OS) rates than men with normal BMIs.

Researchers were surprised to see this, since previous research has linked obesity with the activation of the cancer-promoting IGF-1/PI3K/AKT molecular pathway.

In the 599 patients who received the targeted therapy combination of Tafinlar (dabrafenib) plus Mekinist (trametinib), obese patients demonstrated superior progression-free survival (PFS; 15.7 vs. 9.6 months) and OS (33 vs. 19.8 months) compared with patients with normal BMIs.

This is not the first study to find that higher BMIs could potentially be associated with better survival. Another smaller study, conducted by researchers at the University of Oklahoma Health Science Center, found that obese patients had better outcomes in patients with melanoma, lung and ovarian cancer who were taking anti-PD1 or PD-L1 therapies.

However, in this particular study, which specifically looked at melanoma, obesity did not show the same survival benefit for women, leading researchers to think that the correlation may have to do sex hormones, too.

“The question is, what underlying mechanism causes this advantage in obese men, and can we take advantage of it to improve outcomes in patients with melanoma?” lead author Jennifer McQuade, M.D., instructor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center, said in a press release.

The associations between obesity and better outcomes in certain patients do not necessarily prove causation — so more research is definitely warranted in this field. It should also be noted that obesity may cause more harm than good, and the positive correlation between obesity and melanoma outcomes were only seen for those on targeted therapy or immunotherapy. For patients who were on chemotherapy, no improved outcomes in the obese group were seen.

“The public health message is not that obesity is good. Obesity is a proven risk factor for many diseases,” McQuade said. “Even within our metastatic melanoma population, we would not suggest that patients intentionally gain weight. We need to figure out what is driving this paradox and learn how to use this information to benefit all of our patients.”