P2.03a-001 A Randomized Phase III Clinical Trial of Anlotinib Hydrochloride in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)

Abstract

Anlotinib hydrochloride, a novel multi-targeted tyrosine kinase inhibitor (TKI) was found to exhibit excellent inhibitory efficiency on a variety of receptor tyrosine kinases (RTK) involved in tumor progression, especially the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and stem cell-factor receptor (c-Kit). This ongoing trial aimed at evaluating the efficacy and safety of anlotinib hydrochloride comparing with placebo in advanced NSCLC patients who had received at least two previous chemotherapy and EGFR/ALK targeted therapy regimens. This Phase III, randomized, double-blind, placebo-controlled study (NCT 02388919) is ongoing in 31 centers in China under the supervision of Independent Data Monitoring Committee (IDMC). Pathological stage IIIB/IV adult advanced NSCLC patients (Pts) who had failed with at least two previous chemotherapy and EGFR/ALK targeted therapy regimens were eligible. The status of EGFR and ALK genes should be clear in all enrolled pts. Pts with sensitive EGFR or ALK mutations must had received and appeared intolerance to pervious targeted therapies. Pts were randomized (2:1) to receive Anlotinib hydrochloride or placebo once daily (12 mg) from day 1 to 14 of a 21-day cycle until progression. Dose reduction to 8 or 10 mg/day could be applied when grade 3 or 4 treatment-related toxicities were observed. The minimal sample size was estimated to 450 patients. The primary endpoint is overall survival (OS) and second endpoints are progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and quality of life (QoL). Quality of life was assessed via EORTC QLQ-C30, safety is determined using standard NCI-CTCAE v4.02, and responses are evaluated according to RECIST v1.1. This study started in February 2015, up to early July 2016, a total of 420 pts have been enrolled (93.3 % of 450 pts). Among enrolled pts, about 80 % were diagnosed as adenocarcinoma, EGFR mutation or ALK rearrangement was found in 1/3 of the pts. The overall analyzes will start after 300 OS events. Anti-angiogenesis is the main mechanism of Anlotinib hydrochloride for preventing the tumor progression. Results of randomized, placebo-controlled Phase II trial (NCT01924195) has been reported in WCLC 2015, however, advantages in PFS (4.8 vs. 1.2 months) and OS (9.3 vs. 6.3 months) were observed in Anlotinib arm from the renewed data. Based on these exciting data, we are looking forward for the results of the Phase III trial.