PLATINUM Trial: Preliminary Analysis of Lazertinib Therapy in Locally Advanced, Unresectable, EGFR Mutation(+) NSCLC Following CCRT

초록

Introduction: The PACIFIC trial has demonstrated sustained overall survival (OS) benefit with durvalumab as consolidation therapy after concurrent chemoradiation therapy (CCRT). In a subgroup analysis, the effect was not provenin EGFRmutation positive patients. Lazertinibis 3rd generation EGFR TKI as osimertinib and shows good anti-cancer effect in EGFR sensitive mutations in LASER 301 trial. PALTINUM trial is an ongoing, phase II trial, evaluating the efficacy and safety of lazertinib as consolidative treatment after CCRT in patients who had EGFR mutation positive NSCLC (E19del/ L858R, Stage III). We present data from the preliminary efficacy and safety data. Methods: Eligible patients (18 years) with inoperable stage III EGFR mutation positive NSCLC (AJCC 8th edition), who have not progressed following CCRT, received lazertinib as consolidation therapy. Primary endpoint is PFS and 2ndary endpoints are OS, the objective response rate, the duration of response, the time to death or distant metastasis, and safety. Results: Twenty-five patients enrolled in this analysis. At the 29 Feb 2024 database lock (median follow-up, 12.7 mo), the median age was 67 years, 56% were females, 56% were never smokers. The objective response rate and disease control rate were 72%, 100%, respectively. Among never or former smokers, 50% demonstrated a partial response to lazertinib, indicating significant tumor regression. Conversely, all current smokers exhibited only stable disease, with no cases of partial response observed. Median PFS was not reached. The most common treatmentrelated Grade 3 adverse events (AEs) were dermatitis (8%), paraesthesia (4%), asthenia (4%) and pulmonary embolism (4%). Treatment-related AEs leading to discontinuation occurred in 16% of patients. Grade 2 radiation pneumonitis developed in three patients (12%), but no lazertinibrelated pneumonitis was observed (table). Conclusions: In this preliminary analysis from PLATINUM trial, consolidative lazertinib demonstrated clinically meaningful efficacy and no new safety signal was detected at interim analysis.