Potential Mechanisms


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Dr McQuade described several mechanisms that may explain the protective effect of obese BMI in this population. “Obese patients have more of a metabolic reserve to enable them to better tolerate therapy,” she said, though she noted that melanoma and treatment with immunotherapy or targeted therapy, unlike chemotherapy, do not typically cause weight loss.

Another potential mechanism is the established biological difference between tumors from patients who are obese vs those who have a normal BMI. This difference could affect “how these tumors respond to therapy,” Dr McQuade said. She added that “the magnitude of the difference (doubling of survival in males) and the dose-response we saw between BMI and survival (improved PFS through morbid obesity) would support this.”

Next Steps

Dr McQuade said that the next step in their research is to understand the mechanism underlying the association between obese BMI and better outcomes. “We are asking the basic question: is there a fundamental biological difference between the melanoma in an obese vs a nonobese individual? We are also testing specific hypotheses around hormonal signaling and the immune response.”

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She also noted that “it is too early to make specific recommendations until we understand the mechanism. We certainly don’t have data to support recommending intentional weight loss to our obese male patients with metastatic melanoma.”

Reference

  1. 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. 2018 Feb 12. doi: 10.1016/S1470-2045(18)30078-0 [Epub ahead of print]
  2. Hayes AJ, Larkin J. BMI and outcomes in melanoma: more evidence for the obesity paradox. Lancet Oncol. 2018 Feb 12. doi: 10.1016/S1470-2045(18)30077-9 [Epub ahead of print]