Cisplatin-gemcitabine-durvalumab reintroduction in advanced biliary tract cancer: a multinational real-world analysis

BACKGROUND: Treatment options for advanced biliary tract cancers (BTCs) progressing after first-line chemoimmunotherapy remain limited. Whether platinum-based chemotherapy reintroduction can restore disease control is unknown. This study evaluates cisplatin-gemcitabine-durvalumab (CGD) reintroduction in patients with advanced BTC progressing during durvalumab maintenance. METHODS: A multinational cohort of patients with BTC received first-line CGD followed by durvalumab maintenance. Those progressing during maintenance and treated with CGD reintroduction or FOLFOX/XELOX were analyzed. Primary endpoints were overall survival (OS) and progression-free survival (PFS) in the CGD reintroduction group; secondary endpoints included survival outcomes from maintenance and second-line initiation, overall response rate, and disease control rate. RESULTS: Among 1258 patients treated with first-line CGD, 475 received durvalumab maintenance. After disease progression during maintenance (n = 309, 65.1%), 31 patients (6.5%) underwent CGD reintroduction, while 114 (24%) received FOLFOX/XELOX. Baseline characteristics were comparable between groups, except for bilirubin levels. After a median follow-up of 22.6 months [95% confidence interval (CI) 20.0-25.1], median OS was not reached in the reintroduction cohort, while median PFS was 13.3 months (95% CI 9.7-15.8) from first-line initiation. From durvalumab maintenance start, median OS remained not reached and median PFS was 7.1 months (95% CI 4.8-11.3). Following reintroduction, median OS and PFS were 10.5 months (95% CI 8.0-10.5) and 9.0 months (95% CI 5.5-10.2). Compared with FOLFOX/XELOX, CGD reintroduction was associated with significantly improved OS [hazard ratio (HR) 0.47; P = 0.006] and PFS (HR 0.44; P < 0.0001) from first-line therapy start, as well as improved PFS from second-line treatment start (HR 0.60; P = 0.027). These findings were confirmed after multivariable and inverse probability of treatment weighting adjustment. Response outcomes were comparable between groups. CONCLUSIONS: This is the first study evaluating CGD reintroduction in patients with BTC progressing during durvalumab maintenance. Although the retrospective design does not allow definitive conclusions, our findings suggest potential benefit in selected patients.