Phase 1b Study of Sintilimab Plus Anlotinib as First-line Therapy in Patients With Advanced NSCLC
Tianqing Chu, Runbo Zhong, Hua Zhong, Bo Zhang, Wei Zhang, Chunlei Shi, Jialin Qian, Yanwei Zhang, Qing Chang, Xueyan Zhang, Yu Dong, Jiajun Teng, Zhiqiang Gao, Huiping Qiang, Wei Nie, Yiming Zhao, Yuchen Han, Ya Chen, Baohui Han, Tianqing Chu, Runbo Zhong, Hua Zhong, Bo Zhang, Wei Zhang, Chunlei Shi, Jialin Qian, Yanwei Zhang, Qing Chang, Xueyan Zhang, Yu Dong, Jiajun Teng, Zhiqiang Gao, Huiping Qiang, Wei Nie, Yiming Zhao, Yuchen Han, Ya Chen, Baohui Han
Abstract
Introduction: Although the interaction between tumor immune microenvironment and angiogenesis has been well established, evidence supporting the chemo-free combination of immune checkpoint inhibitors plus antiangiogenic tyrosine kinase inhibitors in treatment-naive patients with advanced NSCLC is insufficient. This report provides the efficacy and safety of sintilimab combined with anlotinib as first-line therapy for advanced NSCLC from a phase 1b trial (NCT03628521).
Methods: Eligible patients who were treatment-naive and had unresectable stage IIIB/C or IV NSCLC without EGFR/ALK/ROS1 mutations received sintilimab (200 mg, day 1) and anlotinib (12 mg, day 1-14) every 3 weeks till disease progression or unacceptable toxicity. Baseline programmed death-ligand 1 expression and tumor mutation burden status was assessed in all patients. The primary end points were objective response rate and safety.
Results: A total of 22 patients received sintilimab and anlotinib. Median follow-up was 15.8 months (range: 8.3-19.3). Sixteen patients achieved confirmed partial response with an objective response rate of 72.7% (95% confidence interval [CI]: 49.8%-89.3%) and disease control rate of 100% (95% CI: 84.6%-100%). Median progression-free survival was 15 months (95% CI: 8.3 m, not reached), and the 12-month progression-free survival rate was 71.4% (95% CI: 47.2%-86.0%). The incidence rate of grade 3 or higher treatment-related adverse events was 54.5%, and grade 3 hypertension was predominant (two of 22, 9.1%). No grade 4 treatment-related adverse events were observed, and one case of grade 5 immune-related pneumonitis occurred.
Conclusions: To the best of our knowledge, this is the first study that assessed an anti-programmed cell death protein 1 antibody combined with a multitarget antiangiogenic tyrosine kinase inhibitor in the frontline setting for patients with NSCLC. In view of its encouraging efficacy, durability, and safety profile, sintilimab plus anlotinib represents a novel chemotherapy-free regimen in this patient population.
Keywords: Antiangiogenic TKIs; Anti–PD-1; Chemotherapy-free; First-line; Non–small cell lung cancer.
Copyright © 2020. Published by Elsevier Inc.
Source: PubMed