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

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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.