A multicenter, randomized, double-blind study of gefitinib in combination with anlotinib or placebo in previously untreated patients with EGFR mutation-positive advanced non-small cell lung cancer (FL-ALTER).

Abstract

TPS9131 Background: Preclinical and clinical evidence has demonstrated that the dual blockade of the EGFR and VEGF pathways is a viable strategy in the EGFR-mutated advanced NSCLC population. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that effectively inhibits VEGFRs, FGFRs, PDGFRs, c-kit and MET. It has been proved to be safe and effective in advanced lung cancer after second-line standard chemotherapy failure. A cohort study of Anlotinib plus Erlotinib has shown a favorable safety profile and promising antitumor activity with an objective response rate (ORR)92.6%. This phase III study aims to evaluate the efficacy and safety of Anlotinib or placebo plus Gefitinib in patients(pts) with untreated EGFR-mutated metastatic NSCLC. Methods: Eligible pts were aged 18̃75 years old, had stage IIIB or IV NSCLC, with an EGFR 19del or 21L858R mutation, an ECOG PS of 0 or 1, measurable lesion according to RECIST v1.1 and adequate organ function. We randomly assigned eligible pts in a 1:1 ratio to receive oral Gefitinib (250 mg QD) plus either Anlotinib (12 mg QD from day 1 to 14 of a 21-day cycle) or matching placebo until progressive disease or unacceptable toxicity. Randomization was done by an interactive web response system with a computer-generated sequence and stratified by EGFR mutation status, gender, ECOG PS and pathological type. The primary endpoint is progression-free survival(PFS). Secondary endpoints include overall survival, ORR, disease control rate, time to progression, duration of response, quality of life and the safety profile. The peripheral blood of the pts will be detected three times by polygenic detection to monitor the resistance mechanism (before treatment, during the first evaluation, during tumor progression, each time 10ml peripheral blood). Independent Data Monitoring Committee and Independent Review Committee will be used in this study. According to previous report (Erlotinib plus Bevacizumab vs. Erlotinib alone: 16.0 vs. 9.7 mos, HR 0.54, Lancet Oncol, 15(11):1236-1244), the sample size was determined based on a median PFS of 15 months for the Anlotinib + Gefitinib group and median PFS of 10 months for the Placebo + Gefitinib group. To achieve 80% power at a two-sided α = 0.05 and an anticipated dropout rate of 20%, 310 patients (with 192 events required for the analyses) were needed. In total, 310 patients will be enrolled in this trial at 16 sites in China. From April 2019, 224 patients have been enrolled. Clinical trial information: NCT04028778.