Associations between obesity and outcomes in pembrolizumab-treated endometrial cancer.

[BACKGROUND] To determine the association between obesity and pembrolizumab response in racially diverse cohort of patients with advanced and recurrent endometrial cancer (EC).

[METHODS] We conducted a retrospective review of patients with advanced or recurrent endometrial cancer receiving pembrolizumab. Baseline clinical, demographic and cancer characteristics were collected. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and modeled via Cox regression. Covariate differences were assessed using the log-rank test.

[RESULTS] Among the 179 patients, the median age was 65 years (IQR, 58-71 yrs) and the mean BMI was 33 (SD, 8.5). The cohort consisted of 55 Black patents (31 %) and 112 White patients (63 %); 99 patients (55 %) were obese. Forty-six patients received pembrolizumab alone, and 133 received combination therapy. Higher BMI was associated with shorter PFS (BMI >40: HR 1.91, CI 1.13-3.21, p = 0.014 and BMI 30-40: HR 1.55, CI 1.02-2.35, p = 0.041). In MMR stratified analysis, obesity was associated with lower response rates among patients with MMRp tumors (23.4 %; BMI ≥30 vs 40.0 %; BMI <30), whereas response remained high across BMI categories in MMRd tumors. In the subgroup treated with pembrolizumab and Lenvatinib (n = 79), both White and Black obese experienced worse PFS compared to White non-obese patients (p = 0.021 and p = 0.035, respectively). No significant differences in OS were observed between obese and non-obese groups.

[CONCLUSIONS] In this diverse cohort, obesity was associated with worse PFS in patients treated with pembrolizumab for EC. MMRp tumors in obese patients had lowest response rates among subgroups. Further studies with long term follow up are needed to elucidate the biological mechanisms linking obesity to immunotherapy outcomes.