P066 A Phase I Study of Apatinib Combined with Pemetrexed and Carboplatin in Untreated EGFR-Negative Stage IV Non-Squamous NSCLC

Abstract

This phase I study aimed to establish the feasible dose of Apatinib in combination with pemetrexed plus carboplatin as first-line therapy for EGFR-negative stage IV non-squamous non-small-cell lung cancer (NSCLC). Using a 3+3 dose-reduction design, patients received oral Apatinib at four dose levels: 750 mg qd, 500 mg qd, 500 mg/day 2 weeks on/1 week off schedule (schedule 2/1) or 250mg qd. Pemetrexed (500 mg/m2) plus carboplatin (AUG=5) was administered every 3 weeks. The feasible dose was determined based on cycle 1 dose-limiting toxicities (DLT); other assessments included safety and antitumor activity according to response evaluation criteria in solid tumors. A total of 12 patients were enrolled and cycle 1 DLTs were observed in two patients at 750 mg qd treatment (both Grade 3 hypertension), two patients at 500 mg qd (Grade 3 hypertension and Grade 3 hand-foot syndrome), and only one of six patients at 500 mg/day schedule 2/1 (Grade 3 hypertension). The most frequently drug-related adverse events were hematological toxicity, hypertension, hand-foot syndrome and hepatic transaminases elevation. Partial response was observed in 4 patients of 11 evaluable patients (ORR 36.4%), and 6 patients exhibited stable disease (DCR 90.9%). In patients with advanced non-squamous NSCLC, the feasible dose of Apatinib given with standard-dose pemetrexed and carboplatin was 500 mg/day schedule 2/1. The schedule was generally well tolerated and demonstrated promising clinical benefit in NSCLC.