Safety and Efficacy of Low-Dosage Apatinib Monotherapy in Advanced Lung Squamous-Cell Carcinoma: A Prospective Cohort Study

BACKGROUND: Lung squamous-cell carcinoma (SqCC) is the second most common histology in non-small-cell lung carcinomas (NSCLCs). The treatment options for advanced lung SqCC are still an unmet medical need. Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), is beneficial in the therapy of advanced NSCLC patients. This study aimed to preliminarily assess the efficacy and safety of low-dosage apatinib in patients with advanced lung SqCC. METHODS: In this single-arm, open-label, investigator-initiated phase II prospective study (ChiCTR1800019808), we enrolled patients aged 54–80 years with platinum-refractory or chemotherapy rejected advanced lung squamous-cell carcinoma. Key exclusion criteria included major blood vessel involvement and gross hemoptysis with an amount of more than 20 mL. Apatinib at an initial dose of 250 mg was administered to patients once daily until disease progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was progression-free survival (PFS) in all patients. We assessed the adverse events according to the treatment received. RESULTS: Thirty-eight patients were enrolled between June 11, 2015 and August 29, 2018. Two patients failed to evaluate treatment efficacy for personal reasons, and thus 36 patients were eligible for evaluation of tumor response to apatinib. Median PFS was 4.9 months (95% CI: 3.0–6.8 months). Six patients achieved partial response (PR); the objective response rate (ORR) was 16.7% (6/36), and the total disease control rate (DCR) was 77.8% (28/36). Followed up to March 2020, 35 of the 38 patients were dead, and the 1-year survival rate was 21.1% (8/38). The median overall survival (OS) was 6.9 months (95% CI: 5.2–8.5 months). The most common adverse events included fatigue (50.0%), hypertension (42.1%), proteinuria (23.7%), loss of appetite (23.1%) and hand-foot reaction (21.1%). No grade 4 adverse effect or drug-related mortality occurred. CONCLUSIONS: Low-dose apatinib monotherapy might be an option for patients with advanced lung squamous-cell carcinoma.