Lazertinib as a frontline treatment in patients with EGFR-mutated advanced non-small cell lung cancer: Long-term follow-up results from LASER201

•Additional frontline options for treating EGFR-mutated NSCLC are required.•Lazertinib showed promising efficacy and safety in LASER201 and LASER301 trial.•Long-term follow-up in LASER201 showed long PFS and OS with frontline lazertinib.•Patients with and without baseline brain metastasis showed clinical benefit.•Lazertinib was well tolerated, consistent with earlier reports. This analysis of the first-line cohort of LASER201 study evaluated the efficacy and safety of lazertinib 240 mg as a frontline therapy for epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non–small cell lung cancer (NSCLC). A total of 43 patients, with EGFR mutation-positive (Exon19Del, n = 24; L858R, n = 18; G719X, n = 1) locally advanced or metastatic NSCLC who had not previously received EGFR tyrosine kinase inhibitor (EGFR TKI) therapy, received once-daily lazertinib 240 mg. EGFR mutation status was confirmed by local or central testing. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review. Secondary efficacy endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), tumor shrinkage, and overall survival (OS). At the primary data cut-off (DCO; January 8, 2021), the ORR was 70 % (95 % confidence interval [CI]: 56.0–83.5), DCR was 86 % (95 % CI: 75.7–96.4) and the median DoR was 23.5 (95 % CI: 12.5–not reached) months. The median PFS was 24.6 (95 % CI: 12.2–30.2) months. At the final DCO (March 30, 2023), the median OS was not estimable and the median follow-up duration for OS was 55.2 [95 % CI: 22.8–55.7] months. OS rates at 36 months and 54 months were 66 % (95 % CI: 47.5–79.3 %) and 55 % (95 % CI: 36.6–70.7 %), respectively. The most commonly reported TEAEs were rash (54 %), diarrhea (47 %), pruritus (35 %), and paresthesia (35 %). No drug-related rash or pruritus TEAEs of grade 3 or higher were reported. Diarrhea and paresthesia of grade 3 or higher were reported in 3 (7 %) and 1 (2 %) patients, respectively. This analysis demonstrated long-term clinical benefit with lazertinib 240 mg in patients with EGFR-mutated NSCLC who had not previously received EGFR TKIs. The safety profile for lazertinib was tolerable and consistent with that previously reported.