The “obesity paradox” suggests that higher body mass index (BMI) is associated with better survival values in metastatic melanoma patients, especially those receiving targeted and immune checkpoint inhibitor therapy. Higher BMI is also associated with higher incidences of treatment-related adverse events. This study assesses whether body mass index is associated with survival outcomes and adverse events in metastatic melanoma patients with systemic therapy.
Patients and methods
This multicentric retrospective study, conducted from March 1, 2013 to April 29, 2019, enrolled adults with unresectable stage III or IV melanoma from the French multicentric prospective cohort-MelBase (NCT02828202). Patients with first-line chemotherapy and targeted and immune therapy were included. Underweight people and those with metastatic mucosal or ocular melanoma were excluded. Body mass index was categorized using the World Health Organization criteria. Co-primary outcomes included the association between body mass index and progression-free survival and overall survival, stratified by treatment type, sex and age. Secondary endpoints were the association of body mass index with overall response and treatment-related adverse events. Multivariate analyses were performed.
Totally, 1,214 patients were analyzed. Their median age was 66.0 years (range, 53-75). Male predominance was observed (n = 738 [61%]). Most patients received immune checkpoint inhibitor therapy (63%), followed by targeted therapy (32%), and had stage M1c disease (60.5%). Obese patients represented 22% of the cohort. The median follow-up duration was 13.5 months (range, 6.0-27.5). In the pooled analysis, no positive or negative association between body mass index and progression-free survival ( p = 0.88)/overall survival ( p = 0.25) was observed, regardless of treatment type, sex, and age. These results were nonsignificant in the univariate and multivariate analyses. The objective response rate, according to body mass index category, did not differ significantly regardless of age. Treatment-related adverse events were not associated with body mass index.
The observed lack of an association between body mass index and survival demonstrates that body mass index is not a valuable marker of systemic treatment-related outcomes in metastatic melanoma. Future approaches might focus on the whole-body distribution.