Abstract 62P
Background
Dual VEGF and EGFR blockade could delay emergence of EGFR TKI resistance and improve clinical outcomes in patients with EGFR-mutant NSCLC. This study was designed to explore the preliminary antitumor activity and safety of firmonertinib (a third-generation EGFR-TKI) combined with anlotinib (a multi-targeting TKI including anti-angiogenetic effects) in patients with treatment-naïve EGFR-mutant NSCLC.
Methods
FOCUS-A was a prospective multicenter phase II study. Forty patients with treatment-naïve, EGFR-mutant, locally advanced or metastatic NSCLC were enrolled. The regimen was firmonertinib (80 mg qd) plus anlotinib (10 mg qd, day 1 to 14 every 21 days). The primary endpoint was investigator-assessed objective response rate (ORR) according to RECIST 1.1. Secondary endpoints included progression-free survival (PFS), Disease Control Rate (DCR), safety, etc.
Results
At data cut-off (6 Dec 2024), 40 eligible patients were enrolled with a median follow-up of 27.8 months. The median age was 63 years (range 40–71). Most patients were female (65%), never smoking (87.5%) and stage IV adenocarcinoma (95%). The ORR was 87.5% (95% CI, 73.2 to 95.8) and DCR was 100%. The median PFS was 25.1 months (95%CI, 17.9 to not reached). Among the 16 (40%) patients with baseline CNS metastases, the ORR was 87.5% (95%CI, 61.7 to 98.5) and DCR was 100%. The median PFS was 25.1 months (95%CI, 13.8 to 33.2). There was no difference in PFS between ex19del and ex21L858R mutations in patients with baseline CNS metastases (not reached vs 25.1 months; HR 0.72; 95%CI 0.18–2.92; p > 0.05). The median CNS PFS in these 16 patients was 33.2 months (95%CI, 17.9 to 33.2). Grade≥3 treatment-related adverse events (TRAE) were observed in 13 (32.5%) patients. The most common grade≥3 TRAEs were hypertension (7.5%) and proteinuria (7.5%).
Conclusions
Firmonertinib combined with anlotinib exhibited durable antitumor activity with tolerable and manageable safety profile in patients with treatment-naive EGFR-mutant NSCLC.
Clinical trial identification
NCT04895930.
Legal entity responsible for the study
The authors.
Funding
Shanghai Allist Pharmaceuticals.
Disclosure
All authors have declared no conflicts of interest.