Apatinib in Patients with Extensive-Stage Small-Cell Lung Cancer After Second or Third-Line Chemotherapy: A Phase II, Single-Arm, Multi-Center, Prospective Study

Abstract

Background: Small-cell lung cancer (SCLC) remains an aggressive cancer with dismal long-term survival due to the limited therapeutic options available after failure of chemotherapy. Apatinib is a novel oral, small-molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor 2. This study aimed to investigate the efficacy and safety of apatinib in patients with extensive-stage (EC) SCLC who had progressed after two or three previous therapies. Methods: This phase II, single-arm, prospective study was conducted at three medical centers in China. Eligible patients were aged 18 years or older and had histologically-confirmed ES-SCLC after two or three previous treatments, including a platinum-based regimen. Patients were assigned to receive oral apatinib at an initial dose of 500 mg once daily. The primary endpoint was the objective response rate (ORR) in both the intention-to-treat (ITT) and per-protocol populations. The safety analysis included all patients who received at least one dose of study medication. Findings: Forty patients were enrolled, all of whom received at least one dose of apatinib. At the data cut off time (Nov 15, 2018), the median follow-up was 7.4 months (IQR 1·0-22·2); no patients remained on treatment, and 5 were still in follow-up. An objective response was achieved in 7 of 40 patients (17.5%) in the ITT population, and 7 of 38 patients (18.4%) in the per-protocol population. The median progression-free survival and overall survival were 3·0 months (95% CI 2·2-3·7) and 5·8 months (95% CI 3·7-7·9), respectively. The median response duration was 2·6 months (95% CI 1·8-3·3). During treatment, apatinib was generally well tolerated, the most commonly observed grade 3 or greater treatment-related adverse events were hypertension (25%; 10/40), hand-foot syndrome (10%; 4/40), increased L gamma-glutamyltransferase (10%; 4/40), increased aspartate transaminase (7·5%; 3/40), and thrombocytopenia (7·5%, 3/40). Interpretation: Apatinib exhibited promising efficacy and an acceptable safety profile in previously heavily-treated patients with ES-SCLC. Further exploration of apatinib in phase III trials is warranted. Clinical Trial Registatration: NCT02945852. Funding Statement: Jiangsu Hengrui Pharmaceuticals Company, China. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The study protocol was approved by the relevant institutional review board or ethics committee at each medical center, and it was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, as defined by the International Conference on Harmonisation. All enrolled patients provided written informed consent before any study-specific procedures were performed.