Baseline body mass index (BMI) impact in advanced cholangiocarcinoma (CCA) treated with chemo-immunotherapy (Chemo-IO): Overall, sex-based, and site-specific analyses.

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e16189 Background: Predictive and prognostic factors in advanced CCA remain limited. Although obesity is a recognized risk factor, an “obesity paradox” with improved outcomes in overweight patients (pts) has been reported in several solid tumors. In addition, sex-related differences in immune responses and tumor site biology may influence the efficacy of immune checkpoint inhibitors (ICI). We evaluated the impact of baseline BMI on outcomes in advanced CCA, overall, by sex and by tumor site. Methods: BMI (kg/m ² ) at initiation of first line (1L) therapy (tx) was recorded. Survival outcomes (overall survival [OS] and progression-free survival [PFS]) were evaluated according to BMI groups and assessed by Kaplan-Meier estimation. Pts were dichotomized as non-overweight (BMI < 25) versus overweight (BMI>25). Additional analyses were conducted using four BMI categories ( < 18.5, 18.5-24.9, 25-29.9 and >30) and further stratified by sex and tumor site. Results: A total of 72 pts were included: 33 (45.8%) males and 39 (54.2%) females. Median age was 66 years (IQR 58-72); median follow-up was 31.6 months (m) (95% CI 18.8-NR). The most common primary tumor site was intrahepatic CCA (iCCA) (37 pts, 51.3%), followed by perihilar CCA (15 pts, 20.8%), gallbladder (11 pts,15.3%) and distal CCA (9 pts, 12.5%). At diagnosis, 66 pts (91.7%) had metastatic disease and 8 (8.3%) locally advance disease. All pts received 1L platinum-gemcitabine plus ICI tx, with 65 pts (90.3%) had an ECOG PS of 0/1 at baseline. Overall, mPFS was 7.1 m (95% CI 6.1-8.6) and mOS was 11.6 m (95% CI 9.9-21.3). Thirty-one pts were overweight and 41 were non-overweight; obesity (BMI>30) was observed in 6 pts (8.3%). Overweight pts had significantly longer mPFS (8.6 vs 6.4 m; HR 0.58, 95% CI 0.28-0.81; p < 0.01), with no significant difference in mOS (12.5 vs 9.9 m; HR 0.56, 95% CI 0.41-1.30; p = 0.30). In analyses by four BMI categories, obesity was independently associated with improved mPFS (HR 0.20, 95% CI 0.05-0.87; p = 0.03). In sex-based subgroup analysis, improved mPFS in overweight pts was statistically significant in females (8.3 vs 5.7 m; HR 0.47, 95% CI 0.23-0.94; p = 0.03), whereas only a trend was observed in males (11.4 vs 6.6 m; HR 0.41, 95% CI 0.17-1.02; p = 0.05). No significant OS differences by BMI were observed in either sex. Overweight was also significantly associated with improved mPFS in iCCA (8 vs 6.1 m; HR 0.35, 95% CI 0.15-0.78; p < 0.01), with no impact on mOS. No significant associations were observed in extrahepatic CCA and gallbladder. Conclusions: Baseline overweight significantly improved PFS in advanced CCA pts treated with chemo-IO, particularly among obese pts, females and iCCA, without a significant impact on OS. Further studies are needed to determine whether BMI, sex, and tumor site may modulate ICI efficacy and guide treatment optimization in selected CCA pts.

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