A Phase II Clinical Trial of Apatinib in Pretreated Advanced Non-squamous Non–small-cell Lung Cancer

Apatinib is an oral multi-tyrosine kinase inhibitor that has been effective in treating many solid tumors. This phase II clinical trial evaluated the efficacy and safety of apatinib in cases of previously heavily treated non-squamous non–small-cell lung cancer. Apatinib showed promising efficacy and manageable toxicity, and thus represents a therapeutic option for patients with non-squamous non–small-cell lung cancer. Objectives: Apatinib exhibits broad-spectrum antitumor activities by selectively inhibiting vascular endothelial growth factor receptor-2. This study evaluated the efficacy and safety of apatinib in patients with advanced non-squamous non–small-cell lung cancer who were heavily pretreated or not suitable to receive standard second-line chemotherapy. Patients and Methods: This was an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT02515435). Patients received 500 or 750 mg apatinib daily until progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was the objective response rate. The secondary endpoints included disease control rate, progression-free survival, overall survival, and side effects. Apatinib administration was allowed beyond disease progression. Results: Between March 2015 and August 2016, 40 patients were enrolled. Among them, 6 (15.0%), 16 (40.0%), and 18 (45.0%) received apatinib as the second-, third-, and fourth-line or beyond treatment, respectively. The mean dosage of apatinib was 477.0 ± 85.3 mg/day. Thirty-eight patients were available for response evaluation; the objective response rate and disease control rate were 13.2% and 63.2%, respectively. The median progression-free survival was 3.06 months (95% confidence interval [CI], 2.20-4.14 months). The median overall survival was 7.69 months (95% CI, 5.36 months to not estimable). The most common treatment-related adverse events were hand-foot-skin reaction (30.0%), proteinuria (27.5%), oral mucositis (22.5%), fatigue (20.0%), and hypertension (17.5%). Nine patients received apatinib after progression, and the median duration of apatinib therapy beyond progression was 5.13 months (95% CI, 4.27-7.82 months). Conclusion: Apatinib shows promising efficacy and manageable toxicity in patients with advanced non-squamous non–small-cell lung cancer. Apatinib therapy beyond progression could provide further benefits in specific subpopulations.