A retrospective cohort study of anti-PD-1 therapy combined with chemotherapy in patients with advanced biliary tract cancer.

Abstract

e14100 Background: Biliary tract cancer (BTC) is highly aggressive with poor prognosis and few treatment options following progression on gemcitabine-based chemotherapy. Disappointing results from clinical trials for refractory BTC highlight the need for more effective therapies. Immune checkpoint inhibitor (ICI) has been hailed as a major breakthrough for cancer treatment. However, evidence for the efficacy of immunotherapy in biliary tract cancer (BTC) is limited and unsatisfactory. KEYNOTE-158 trial has merely shown a 5.8% of overall response rate with pembrolizumab monotherapy in advanced BTCs. Thus, combining other therapies with ICIs is becoming the researching focus. Herein, we constructed a cohort to evaluate the efficacy and safety of ICIs combined with chemotherapy in advanced BTCs. Methods: Chinese BTC patients receiving PD-1 inhibitors with chemotherapy, PD-1 inhibitors monotherapy or chemotherapy alone were retrospectively analyzed. The primary outcome was overall survival (OS). The key secondary outcome were progression-free survival (PFS) and safety. Patients previously treated with any agent targeting T-cell co-stimulation or immune checkpoints were excluded. Results: The study included 77 patients (PD-1 inhibitors plus chemotherapy, n = 38; PD-1 inhibitors monotherapy, n = 20; chemotherapy, n = 19). Median OS was 14.9 months with PD-1 inhibitors plus chemotherapy, 4.1 months with PD-1 inhibitors and 6.0 months with chemotherapy, with significantly longer for anti-PD-1 combination therapy than monotherapy (HR 0.37, 95% CI 0.17-0.80, P= 0.001) or chemotherapy (HR 0.63, 95% CI 0.42-0.94, P= 0.011). Median PFS was 5.1 months with PD-1 inhibitors plus chemotherapy, 2.2 months with PD-1 inhibitors and 2.4 months with chemotherapy, with significant difference for anti-PD-1 combination therapy versus anti-PD-1 monotherapy (HR 0.59, 95% CI 0.31-1.10, P= 0.014) or chemotherapy (HR 0.61, 95% CI 0.45-0.83, P= 0.003). Grade 3 or 4 treatment-related adverse events were similar between anti-PD-1 combination group and chemotherapy group (34.2% and 36.8%). Conclusions: PD-1 inhibitors plus chemotherapy is effective and tolerable for advanced BTC.