Apatinib Plus Vinorelbine in Second Line Treatment Failure Wildtype Advanced Non-Small Cell Lung Cancer (VICTOR): A Phase II Three-Dimensional Co-Culture Platforms-Guided Prospective Study

Background: We aimed to assess the efficacy and safety of apatinib combined with oral vinorelbine in these patients using a prospective three-dimensional co-culture platform. Methods: During the three-dimensional co-culture platform based susceptibility test in vitro, apatinib in combination with vinorelbine has been found to have promising activity and, therefore, was evaluated in a perspective phase II trial. 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. Findings: Preliminary drug susceptibility tests among 3 patients with second line treatment failure non-driver mutation advanced NSCLC verified the combinatorial efficacy of apatinib combined with vinorelbine. Twenty-five patients completed the treatment, while five discontinued treatment due to 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 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. Interpretation: Our study demonstrates that apatinib combined with oral vinorelbine is an effective option with an acceptable safety profile in non-driver gene mutation advanced NSCLC patients refractory to two or more lines of prior chemotherapy. This suggests the feasibility of three-dimensional co-culture platform models to guide prospective clinical research. Trial Registration: NCT03652857 (VICTOR). ORCID：0000-0002-6829-7176. Funding Statement: This work was supported by the National Natural Science Foundation of China (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 Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: Institutional review board approval was obtained from Hunan Cancer Hospital IRB Committee. Patient consent was obtained.