Anlotinib（Catequentinib） is an oral multi-targeted tyrosine kinase inhibitor that effectively inhibits VEGFRs, FGFRs, PGFRs, c-kit and MET. 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.
Eligible pts were aged 18∼75 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 (G+A group, 12 mg QD, days1-14, 21days per cycle) or matching placebo(G+P group) until progressive disease or unacceptable toxicity. The primary endpoint was PFS assessed by IRC. Secondary endpoints included OS、ORR、DCR、DoR and safety. Blood samples for ctDNA analysis were collected at baseline, first evaluation, and progression disease (PD) and analyzed with a 329-gene panel.
From Apr. 2019 to Aug. 2021, 315 patients were assigned to the G+A (n=157) or G+P group (n=158). At data cutoff (Jul 31, 2022), the median follow-up was 17.3m in G+A and 18.8m in G+P. The mPFS by IRC was significantly longer in G+A than in G+P group (14.75m vs. 11.20m; HR 0.64, p = 0.0035). Confirmed ORR was 76.13% in G+A and 64.52% in G+P. Treatment with G+A was associated with more durable response (mDoR: 12.48m vs 9.46m, HR=0.56, p=0.0003) than G+P. OS data are immature. Grade ≥3 TEAEs occurred in 49.68% (G+A) vs. 30.97% (G+P). The most common Grade ≥3 TEAEs were hypertension (29.68 %) in G+A and increased ALT (12.26%) in G+P. We also exploratory analysis biomarker information and resistance mechanism based on dynamic ctDNA. The preliminary analysis of the ctDNA data of 289 pts showed that pts with TP53+EGFR CNV co-mutations had a better benefit from G+A than G+P (11.74 m vs 6.83m; HR=0.3). We will update the detailed biomarker data in congress.
Compared with G+P group, G+A group significantly prolonged PFS in pts with untreated metastatic EGFR-mutated NSCLC and the safety profiles were manageable.
Clinical trial identification
Legal entity responsible for the study
1) Chia Tai-Tianqing Pharmaceutical Co., Ltd. 2) OrigiMed.
All authors have declared no conflicts of interest.