P3.02c-025 Safety and Efficacy of Apatinib in Patients with Previously Heavily Treated Advanced Non-Squamous Non-Small-Cell Lung Cancer: Topic: Targeted Therapy

Abstract

Apatinib is a tyrosine kinase inhibitor which selectively inhibits VEGFR-2 and also represents mild inhibition to PDGFR, c-Kit and c-src. It is an orally bioavailable, small molecule agent which is thought to inhibit angiogenesis and tumor cell proliferation. Previous clinical trials have demonstrated its obvious antitumor activity in various cancer type. Thus we designed this phase II, open-label, single-armed, prospective study (NCT02515435) to investigate the efficacy and safety of apatinib for heavily treated, advanced non-squamous NSCLC patients who are not applicable to current standardized therapy or other clinical trials. We prospectively enrolled 40 patients with previously heavily treated advanced non-squamous NSCLC. All patients received apatinib with a dose of 500mg, q.d., p.o. Efficiency was evaluated initially 4 weeks later and then every 8 weeks until disease progression, death, or unacceptable toxicity. The primary end point of this study was overall response rate (ORR). The secondary end points were progression-free survival (PFS), overall survival (OS). Forty patients were enrolled in the study with a median age of 61. 15% of patients received apatinib as second-line therapy, 40% of patients received apatinib as third-line therapy, and 60% as forth-line to twelfth-line therapy. Nine patients were found with activated EGFR mutation. Among all the enrolled patients, 38 patients had clinical evaluation and the other 2 received treatment of apatinib less than one month. Within 33 patients who had available image efficiency, 6 were identified as PR,17 SD and 10 PD, no CR was observed. The ORR was 18.18 %, the DCR was 69.69%. The ORR for patients with EGFR mutation positive and negative were 25% and 16% separately. The median PFS was 3.22 months (95% CI, 2.20-4.17 months). Among them, 6 patients received the treatment of apatinib more than five months. The 6-month OS rate was 76.98% (95% CI, 61.68%-92.27%), the 12-month OS rate was 57.48% (95% CI, 28.75%-86.20%). Common treatment-related adverse events were proteinuria (25%), hypertension (17.5%), and hand-foot-skin reaction (HFSR)(27.5%). Severe adverse events included grade 3 hypertension (5%), HFSR (5%), and thrombocytopenia (5%), no grade 4 or 5 adverse events were observed. No un-expected adverse events were found. Apatinib as a monotherapy had a promising overall response together with an acceptable side effect in patients with previously heavily treated advanced non-squamous NSCLC. A phase III study comparing apatinib monotherapy with placebo as 3rd/4th setting in advanced non-squamous NSCLC is ongoing to further evaluated the efficacy of apatinib (NCT02332512).