Efficacy and Safety of PD-1 Inhibitor SHR-1210 With Chemoradiotherapy in Locally Advanced Cholangiocarcinoma

Abstract

<h3>Purpose/Objective(s)</h3> To preliminarily evaluate the efficacy and safety of adding PD-1 inhibitor SHR-1210 to chemoradiotherapy in patients with locally advanced cholangiocarcinoma. <h3>Materials/Methods</h3> Patients with confirmed diagnosis of locally advanced cholangiocarcinoma based on histopathological and radiological features were included in the study. Patients received a total dose of 50–60 Gy in 25–30 fractions with concurrent capecitabine (825 mg/m², po, bid) and SHR-1210 (200mg, iv, q2w) on days of radiation. Further consolidation chemotherapy was initiated after completion of radiotherapy and included 4 cycles of gemcitabine (1000 mg/m², iv, Day 1, 8) and cisplatin (75 mg/m², iv, with total volume divided at Day 1-3) in a 21-day cycle with SHR-1210 (200mg, iv, q3w). All patients received study treatment until SHR-1210 was administered for up to 12 months or until disease progression, unacceptable toxicity, or withdrawal of consent. <h3>Results</h3> From November 2019 to October 2020, 10 patients were enrolled in the study (6 male [60%], median age, 56 [range, 50-66] years, 4 IIIb stage, 6 IIIc stage). All patients completed radiotherapy. Six patients (60%) experienced myelosuppression, including two with grade 4 advert events (AEs), one stopped chemotherapy and one stopped study treatment. Four patients (40%) developed grade 2 gastrointestinal tract reactions, and the incidence of grade ≤ 3 reactive cutaneous capillary endothelial proliferation (RCCEP) was 100%. All patients had an apparent decrease in the tumor markers CEA and CA-199 levels with symptoms significantly relieved as response to treatment. Among 10 patients treated, 0 (0%) exhibited complete response (CR), 5 (50%) exhibited partial response (PR), 4 (40%) exhibited stable disease (SD) and 1 (10%) exhibited disease progression (PD). The 6-month progression-free survival rate (PFS) was 90%. <h3>Conclusion</h3> These findings suggest that combined treatment with PD-1inhibitors and chemoradiotherapy for locally advanced cholangiocarcinoma is tolerable and effective, which provides a new strategy for the treatment of locally advanced cholangiocarcinoma.