Efficacy and Safety of Apatinib Plus Vinorelbine in Patients With Wild-Type Advanced Non-Small Cell Lung Cancer After Second-Line Treatment Failure: A Nonrandomized Clinical Trial.

Importance: There is currently no standard treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) without driver gene variation after failure of 2 or more lines of chemotherapy. Objective: To assess the efficacy and safety of apatinib combined with oral vinorelbine. Design, Setting, and Participants: This phase 2 prospective nonrandomized clinical trial evaluating the efficacy and safety of apatinib plus vinorelbine recruited patients from Hunan Cancer Center, Hunan, China, from January 1, 2017, to November 30, 2018. Eligible patients were those with wild-type advanced NSCLC whose disease did not respond to at least 2 lines of chemotherapy. Patients were evaluated until December 31, 2019. Data were analyzed from July 2019 to December 2019. Intervention: Apatinib at an initial dose of 500 mg once daily and oral vinorelbine 60 mg/m2 once weekly were administered until disease progression, patient withdrawal, or occurrence of unacceptable toxic effects. Main Outcomes and Measures: The primary end point was overall response rate. Secondary end points were overall survival, progression-free survival, and safety. Results: The potential efficacy of apatinib plus vinorelbine was identified using drug susceptibility assay based on 3-dimensional coculture of tumor cells derived from 3 patients with lung adenocarcinoma. Among 30 patients enrolled, the median (range) age was 63 (34-78) years and 18 (60%) were men. Most patients (27 patients [90%]) had stage IV disease, and the median (range) number of prior unsuccessful treatments was 2 (2-5) lines of chemotherapy. Twenty-five patients (83%) completed the treatment, while 5 patients (17%) discontinued treatment owing to intolerable adverse events. The overall response rate was 36.7% (11 patients) and the disease control rate was 76.7% (23 patients). The median progression-free survival was 4.5 (95% CI, 2.4-6.6) months, and the median overall survival was 10.0 (95% CI, 4.8-17.1) months. Hand-foot syndrome was the most common adverse event observed, including grade 3 hand-foot syndrome observed in 5 patients (17%) and grade 4 hand-foot observed in 1 patient (3%). Grade 3 weakness was observed in 1 patient (3%). Conclusions and Relevance: These findings suggest that apatinib combined with oral vinorelbine is a potentially effective regimen with an acceptable safety profile. This regimen may have potential as a treatment option for patients with wild-type advanced NSCLC whose disease failed at least 2 prior lines of chemotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03652857.