Sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma: A prospective, open-label, single-arm, phase II clinical study

Dailong Li, Lu Xu, Jinxing Ji, Dan Bao, Juan Hu, Ying Qian, Yinjie Zhou, Zhuo Chen, Daojun Li, Xiaopeng Li, Xiaoling Zhang, Hao Wang, Changjun Yi, Menglu Shi, Yaqi Pang, Siqi Liu, Xinhua Xu, Dailong Li, Lu Xu, Jinxing Ji, Dan Bao, Juan Hu, Ying Qian, Yinjie Zhou, Zhuo Chen, Daojun Li, Xiaopeng Li, Xiaoling Zhang, Hao Wang, Changjun Yi, Menglu Shi, Yaqi Pang, Siqi Liu, Xinhua Xu

Abstract

Objective: To evaluate the efficacy and safety of sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma (HCC) to provide a more effective first-line treatment for patients with advanced HCC.

Methods: This open-label, prospective, phase II study included patients with unresectable HCC who did not receive systematic treatment. The patients were treated with sintilimab (200 mg, intravenous drip, once every 3 weeks) combined with apatinib (250 mg, oral administration, once a day) plus capecitabine (1000 mg/m2, twice a day; after 2 weeks of oral administration, the drug was stopped for 1 week; course of treatment, 3 weeks). The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety.

Results: Forty-seven patients (1 lost to follow-up) were enrolled in the study. As of March 1, 2022, the ORR and DCR were 50.0% (95% CI: 34.9-65.1%) and 91.3% (95% CI: 79.2-97.6%), respectively, after blind, independent imaging evaluation. The median follow-up time was 18.7 months (95% CI: 17.2-20.2 months). The median PFS was 9.0 months (95% CI: 7.1-10.9 months). The median DoR was 10.8 months (95% CI: 4.8-16.8 months). The median OS was not reached, and the 1-year OS rate was 71.7% (95% CI: 56.5-84.0%). Only 28.3% (13/46) of patients had grade 3/4 treatment-related adverse events.

Conclusion: Sintilimab combined with apatinib plus capecitabine has good safety and anti-tumor activity as a first-line treatment for unresectable HCC. This is worthy of further multi-center, prospective, randomized, large-sample clinical studies.

Clinical trial registration: https://ClinicalTrials.gov, identifier NCT04411706.

Keywords: apatinib; capecitabine; first-line treatment; hepatocellular carcinoma; immune checkpoint inhibitors; sintilimab.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Li, Xu, Ji, Bao, Hu, Qian, Zhou, Chen, Li, Li, Zhang, Wang, Yi, Shi, Pang, Liu and Xu.

Figures

Figure 1
Figure 1
Trial flow diagram.
Figure 2
Figure 2
Waterfall plots of best changes in the size of the target lesion versus baseline.
Figure 3
Figure 3
Swimmers plot of time on treatment for patients who achieved PR.
Figure 4
Figure 4
Kaplan–Meier plot of progression-free survival.
Figure 5
Figure 5
Kaplan–Meier plot of overall survival.
Figure 6
Figure 6
The relationship between PD-L1 expression and progression-free survival.
Figure 7
Figure 7
The relationship between PD-L1 expression and overall survival.

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