Outcomes by antibiotic use in participants with advanced biliary tract cancer treated with durvalumab or placebo plus gemcitabine and cisplatin in the phase 3 TOPAZ-1 study

550 Background: TOPAZ-1 (NCT03875235) is a double-blind, Phase 3 study of durvalumab (D), an immune checkpoint inhibitor (ICI), + gemcitabine and cisplatin (GC) in participants (pts) with advanced biliary tract cancer (BTC). D + GC improved overall survival (OS) in pts with advanced BTC versus placebo (PBO) + GC (Oh et al. NEJM Evid 2022). Use of antibiotics during ICI treatment has been correlated with poorer OS and progression-free survival (PFS; Jiang et al. Front Oncol 2022). Methods: Pts were randomized 1:1 to receive D (1500 mg) or PBO on Day 1 every 3 weeks (Q3W), + G (1000 mg/m2) and C (25 mg/m2) on Days 1 and 8 Q3W, for ≤8 cycles, followed by D or PBO monotherapy Q4W. This exploratory subgroup analysis of TOPAZ-1 assessed OS and PFS by systemic antibiotic use during the study (≥1 dose 14 days before first D/PBO dose to 14 days after last D/PBO dose). Hazard ratios (HRs) were estimated using an unstratified Cox proportional hazards model, adjusting for disease status (initially unresectable or recurrent) and primary tumor location (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer). Data cut-off at primary analysis was Aug 11, 2021. Results: The number (%) of pts using antibiotics during the study (D + GC, 167/341 [49.0%]; PBO + GC, 167/344 [48.5%]) was similar between treatment arms. In the D + GC arm, median OS (95% CI) was similar regardless of antibiotics use: 12.6 (9.7–14.8) months in pts with antibiotics use vs 13.0 (10.8–14.7) months in pts without (Table). In the PBO + GC arm, median OS (95% CI) was 10.3 (8.7–12.5) in pts with antibiotics use vs 12.1 (11.0–13.8) in pts without. OS HRs (95% CI) in D + GC vs PBO + GC were 0.78 (0.59–1.02) in pts with antibiotics and 0.81 (0.62–1.07) in pts without. Median PFS (95% CI) was 7.3 (6.5–7.7) months in pts with antibiotics use vs 7.2 (5.9–7.4) months in pts without in the D + GC arm and 5.7 (5.4–6.6) months vs 6.1 (5.6–7.3) months, respectively, in the PBO + GC arm (Table). PFS HRs (95% CI) were 0.70 (0.55–0.89) in pts with antibiotics use and 0.82 (0.65–1.03) in pts without. Conclusions: In the TOPAZ-1 study of D in BTC, no meaningful difference was found in OS or PFS for participants who received antibiotics during the study period compared with those who did not, and results were consistent with the primary analysis. These results support that people receiving D may be treated with antibiotics when clinically indicated. Clinical trial information: NCT03875235 . [Table: see text]