Obesity Paradox Highlighted Among Some Metastatic Melanoma Patients

Men undergoing targeted treatment or immunotherapy for metastatic melanoma may have better survival outcomes if they are obese

medwireNews: Among patients receiving treatment for metastatic melanoma, obese men undergoing targeted therapy or immunotherapy may have the highest rates of survival, research suggests.

Pooled data for 1918 patients undergoing targeted therapy, immunotherapy or chemotherapy between 2006 and 2016 indicate that an obese body mass index (BMI) was associated with improved progression-free survival (PFS; adjusted hazard ratio [HR]=0.77) and overall survival (OS; HR=0.74) compared with patients with a healthy BMI.

Analysis showed, however, that obesity was only associated with improved PFS and OS for patients undergoing combined targeted therapy, with BRAF plus MEK inhibitors (HR=0.72 and 0.60, respectively), and for those receiving anti-CTLA-4, anti-PD-1 or anti-PD-L1 immunotherapy (HR=0.75 and 0.64, respectively).

No such relationship between obesity and survival was found among patients who received dacarbazine chemotherapy, report Jennifer McQuade, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-investigators.

Furthermore, a significant relationship between BMI and OS from use of targeted or immunotherapies was uncovered among men (HR=0.53), but this association was not found for women.

The authors note that their analysis took into consideration traditional prognostic factors, as well as use of concomitant medications that could alter anti-cancer activity, such as statins or aspirin. 

“Our results have implications for the design of future clinical trials for patients with metastatic melanoma”, the team writes in The Lancet Oncology

They continue: “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.” 

In an accompanying comment, Andrew Hayes and James Larkin, from the Royal Marsden NHS Trust in London, UK, agree that the research adds to wider evidence of an “obesity paradox” but caution that the current findings are restricted to a specific subgroup of metastatic melanoma patients and should not be “extrapolated further”. 

Nevertheless, they believe that “some overweight patients with melanoma who are under active treatment might be reassured that the oft cited negative association of obesity with cancer outcome does not apply to them at that point in time.” 


McQuade JL, Daniel CR, Hess KR, et al. Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis. Lancet Oncol; Advance online publication 12 February 2018 . DOI: https://doi.org/10.1016/S1470-2045(18)30078-0  

Hayes AJ, Larkin J. BMI and outcomes in melanoma: more evidence for the obesity paradox. Lancet Oncol; Advance online publication 12 February 2018 . DOI: https://doi.org/10.1016/S1470-2045(18)30077-9