PD-1 Inhibitors Could Improve the Efficacy of Chemotherapy as First-Line Treatment in Biliary Tract Cancers: A Propensity Score Matching Based Analysis

Miaomiao Gou; Yong Zhang; Tiee Liu; Haiyan Si; Zhikuan Wang; Huan Yan; Niansong Qian; Guanghai Dai

doi:10.3389/fonc.2021.648068

PD-1 Inhibitors Could Improve the Efficacy of Chemotherapy as First-Line Treatment in Biliary Tract Cancers: A Propensity Score Matching Based Analysis

Front Oncol. 2021 Jun 17:11:648068. doi: 10.3389/fonc.2021.648068. eCollection 2021.

Authors

Miaomiao Gou¹, Yong Zhang², Tiee Liu¹, Haiyan Si¹, Zhikuan Wang¹, Huan Yan¹, Niansong Qian^{1

3}, Guanghai Dai¹

Affiliations

¹ Medical Oncology Department, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
² Medical Oncology Department, The Second Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
³ The Hainan Medical Center, Chinese People's Liberation Army General Hospital, Sanya, China.

Abstract

Background: There are limited treatment options for advanced biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer. We compared the efficacy and safety of PD-1 inhibitors plus chemotherapy and chemotherapy alone as first-line treatment in patients with advanced BTC.

Methods: We retrospectively reviewed patients with BTC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor with chemotherapy (anti-PD-1+C group) or chemotherapy alone (C group). Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) was analyzed using Kaplan-Meier survival curves with log-rank tests. Objective response rate (ORR), disease control rate (DCR), and safety were also analyzed.

Results: This study included 75 patients who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) plus chemotherapy and 59 patients who received chemotherapy alone. After matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 5.8m in the anti-PD-1+C group, which was significantly longer than the C group, at 3.2m (HR: 0.47, 95% CI 0.29 to 0.76, P = 0.004). The ORR was 21.7% and DCR was 80.4% in the anti-PD-1+C group, while the ORR was 15.2% and DCR was 69.6% in the C group. No significant differences were found in the ORR and DCR between the two groups (P=0.423, P=0.231). Grade 3 or 4 treatment was related to adverse events (AEs) that occurred in the anti-PD-1+C group, namely hypothyroidism (n=3, 6.5%), rash (n=2, 4.2%), and hepatitis (n=1, 2.2%). There was no AE-related death. The grade 3-4 leukopenia rate was similar in the two groups (4.3% vs. 6.5%).

Conclusions: Anti-PD-1 therapy plus chemotherapy prolonged the PFS compared with chemotherapy alone in advanced BTC with controllable AEs. Further clinical trials are needed to confirm this result.

Keywords: BTC; PD-1 inhibitor; PMS; chemotherapy; immunotherapy.