The Combination of Radiation Therapy and Immunotherapy Is Effective and Well-Tolerated for Unresectable Biliary Tract Cancer.

PURPOSE:For unresectable biliary tract cancer (BTC), chemotherapy (CT) alone is associated with poor survival and severe toxicity. Immunotherapy (IO) is potentially effective for BTC, and radiation therapy (RT) may synergize with IO. We investigated CT versus combined RT and anti-programmed cell death-1 (PD-1) IO for unresectable BTC. METHODS AND MATERIALS:We prospectively observed 117 participants with unresectable BTC either at initial diagnosis or at first recurrence at a single center who chose 1 of 2 treatment options between August 2018 and October 2020. The options were (1) external beam RT combined with anti-PD-1 IO (RT/IO) or (2) CT alone. In the RT/IO group, camrelizumab (200 mg intravenously every 3 weeks) was initiated within 7 days after the completion of RT and continued until progression or intolerable side effects were noted. The median dose per fraction was 55 Gy/25 fractions (range, 50-60 Gy/20-25 fractions). In the CT group, cisplatin and gemcitabine were delivered intravenously every 3 weeks for 8 cycles. We analyzed the adverse events (AEs), overall survival (OS), and disease-free survival (DFS), and performed subgroup analysis according to tumor mutational burden (TMB) and microsatellite status in the combination group. RESULTS:Thirty-nine and 78 participants received RT/IO and CT, respectively. The crude rate of severe AEs (grade ≥3 AEs) was higher in the CT group (79.4% vs 7.7%, P < .001). The OS and DFS after RT/IO were longer than that after CT (median OS: 17.0 vs 11.5 months, P = .01; median DFS: 12.5 vs 7.9 months, P = .008). Participants with low TMB or microsatellite stability had a shorter median OS (13.6 vs 25.7 months, P = .03) and median DFS (9.8 vs 19.3 months, P = .012) than participants with high TMB or microsatellite instability. CONCLUSIONS:RT combined with anti-PD-1 IO may be well tolerated and associated with an improved response rate, DFS, and OS compared with CT alone in patients with unresectable BTC.