Dr Le on the Prevalence of EGFR PACC Mutations in NSCLC

“EGFR PACC mutations are a new classification that [we] defined a few years ago. The new classification is based on the structure and drug response; therefore it can guide clinical treatment opportunities.”

Xiuning Le, MD, PhD, associate professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Internal Medicine at The University of Texas MD Anderson Cancer Center, discussed the prevalence of EGFR PACC mutations in patients with non–small cell lung cancer (NSCLC).

EGFR PACC mutations are a new classification that was defined by investigators from MD Anderson, Le began. The classification is based on structure and drug response and can be used to guide treatment opportunities, she added. EGFR PACC mutations are present in approximately 12% of patients with EGFR-mutated NSCLC, she noted. New therapies are needed to treat patients with disease harboring this specific EGFR mutation, Le noted.

During the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer, Le and colleagues presented data in a poster from the EGFR PACC–mutated cohort of the phase 2 FURTHER trial (FURMO-002; NCT05364073). FURTHER examined the EGFR inhibitor firmonertinib (formerly furmonertinib) in patients with locally advanced or metastatic NSCLC.

At a median follow-up of 16.5 months (95% CI, 14.6-16.6), findings from the study demonstrated that the best objective response rate (ORR) per blinded independent central review was 81.8% (95% CI, 59.7%-94.8%), and the confirmed ORR (cORR) was 68.2% (95% CI, 45.1%-86.1%) among efficacy-evaluable patients who received first-line firmonertinib at 240 mg once daily (n = 22). No complete responses or instances of disease progression occurred. The median duration of response (DOR) was 14.6 months, and the disease control rate was 100% (95% CI, 84.6%-100%). The median progression-free survival (PFS) was 16.0 months (95% CI, 11.0-not reached [NR]).

When given at a daily dose of 160 mg (n = 23), firmonertinib produced a best ORR of 52.2% (95% CI, 30.6%-73.2%) and a cORR of 43.5% (95% CI, 23.2%-65.5%). The DCR was 91.3% (95% CI, 72.0%-98.9%), and patients experienced a median PFS of 11.1 months (95% CI, 6.6-NR). The median DOR was NR.

In terms of safety, any-grade treatment-related adverse effects (TRAEs) were reported at a rate of 96.6% among safety-evaluable patients with EGFR PACC mutations who received the 240-mg dose (n = 29). Grade 3 or higher TRAEs occurred in 20.7% of patients.