Apatinib Combined with Vinorelbine in Second Line Treatment Failure Non-Driver Mutation Advanced Non-Small Cell Lung Cancer(VICTOR): A Phase 2, Single-Arm, Prospective Study

Background: There is currently no standard treatment strategy for non-driver gene mutation advanced non-small cell lung cancer (NSCLC) patients experiencing progression after two or more lines of chemotherapy. Our study aimed to assess the efficacy and safety of apatinib combined with vinorelbine in non-driver gene advanced NSCLC patients for whom at least two lines of prior chemotherapy had failed. Methods: In this phase 2, single-arm, prospective study, we recruited 30 patients with second line treatment failure non-driver mutation advanced NSCLC at Hunan Cancer Hospital (China). The treatment consisted of apatinib at an initial dose of 500 mg once daily on a continuous basis, and oral vinorelbine 60mg/m2 po qweek. Oral apatinib and vinorelbine were continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoint was overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary endpoints were overall (OS), progression-free survival (PFS), disease control rate (DCR) and safety. Safety analyses included enrolled patients who had received at least one dose of study medication. This study is registered with ClinicalTrials.gov, number NCT03652857 (VICTOR). Findings: Between January 2017 and November 2018, 30 patients were enrolled. 25 patients finished all the treatment. 5 patients discontinued the treatment for intolerable adverse events. The ORR and DCR of all the patients was 36.7 %( 11/30) and 76.7 %(23/30) respectively. The median PFS of all the patients was 4.5 months (95% CI 1.9-6.1m). The median OS of all the patients was 11 months (95% CI 3.8m-16.2m). The most common grade 3 to 4 adverse events were non-hematologic including hand-foot syndrome. Conclusion: These data proved that apatinib in combination with vinorelbine is an effective option for an acceptable safety profile in non-driver gene mutation advanced NSCLC patients refractory to two or more lines of prior chemotherapy. Funding: This work was supported by the National Natural Science Foundation (NO.81401902 to Yongchang Zhang, 81702843 to Qing Xia and NO.81501992 to Rui Guan) and the Hunan Natural Science Foundation (2018RS3106 to Yongchang Zhang, 2018JJ2238 to Yongchang Zhang and 2017SK2134 to Nong Yang). Declaration of Interest: None declared. Ethical Approval: Institutional review board approval was obtained from Hunan Cancer Hospital IRB Committee.