Comparative real-world outcomes of durvalumab plus gemcitabine/cisplatin versus pembrolizumab plus gemcitabine/cisplatin as first-line therapy for advanced biliary tract cancer.

133 Background: Durvalumab plus gemcitabine/cisplatin (D+GC; TOPAZ-1) and pembrolizumab plus gemcitabine/cisplatin (P+GC; KEYNOTE-966) are both NCCN Category 1 preferred first-line regimens for advanced biliary tract cancer (BTC). No randomized head-to-head trial comparing these two chemoimmunotherapy regimens exists, and real-world comparative data remain limited. We compared survival and safety outcomes between D+GC and P+GC using a large federated electronic health records network. Methods: Using the TriNetX Global Collaborative Network, we identified adults with BTC (ICD-10: C22.1, C24.0, C23, C24.1) who received durvalumab or pembrolizumab as index therapy with gemcitabine/cisplatin within 30 days. 1:1 PSM balanced cohorts on age, sex, race/ethnicity, BTC subtype, modified Charlson comorbidities, and baseline labs (albumin, bilirubin, CA 19-9, creatinine, hemoglobin). OS was assessed by Kaplan-Meier analysis with log-rank testing. Safety was evaluated as risk of adverse events after index. Results: Before PSM, 3,220 received D+GC and 317 received P+GC; after matching, 246 remained per arm. Median follow-up was 270 days (D+GC) and 204 days (P+GC). Outcomes are shown in Table 1. Conclusions: In this PSM real-world analysis, D+GC and P+GC demonstrated comparable OS as first-line therapy for advanced BTC. P+GC was associated with significantly lower rates of thrombocytopenia, anemia, renal injury, and hospitalizations. These findings suggest a potentially favorable tolerability profile with P+GC that may inform treatment selection. Prospective comparative studies are warranted. Outcome D+GC (n=246) P+GC (n=246) HR/OR (95% CI) P value Median OS, days 461 377 HR 1.15 (0.88–1.52) 0.305 Mortality risk 42.8% 41.8% OR 0.96 (0.67–1.38) 0.824 Thrombocytopenia 35.5% 22.8% OR 0.54 (0.35–0.81) 0.003 Anemia 48.0% 35.2% OR 0.59 (0.38–0.91) 0.017 Renal injury 29.6% 17.8% OR 0.51 (0.32–0.81) 0.004 Hospitalization 47.7% 30.7% OR 0.49 (0.25–0.93) 0.028 Nausea/vomiting 33.1% 23.9% OR 0.63 (0.38–1.05) 0.073 Neutropenia 16.2% 16.3% OR 1.01 (0.61–1.66) 0.972 Rash 7.7% 7.2% OR 0.92 (0.45–1.90) 0.828 Hypothyroidism 7.8% 5.7% OR 0.72 (0.34–1.56) 0.406 HR/OR reported as P+GC vs D+GC. HR >1 indicates higher hazard with P+GC.