WCLC 2025 - Posters & ePosters-P3.12.67 Redefining Tolerability: A Head-To-Head IPD Toxicity Comparison of Amivantamab+Lazertinib vs Osimertinib+Chemotherapy in EGFR-Mutant NSCLC

P3.12.67 Redefining Tolerability: A Head-To-Head IPD Toxicity Comparison of Amivantamab+Lazertinib vs Osimertinib+Chemotherapy in EGFR-Mutant NSCLC

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This individual patient data (IPD) meta-analysis compares the safety profiles of two first-line treatments for EGFR-mutant non-small cell lung cancer (NSCLC): amivantamab plus lazertinib (AMILAZ) and osimertinib combined with platinum-based chemotherapy (OSICT). Data were pooled from the MARIPOSA (AMILAZ, n=429) and FLAURA2 (OSICT, n=276) phase III trials. Baseline characteristics were balanced, with median age 64, 56% female, and 60% ECOG performance status 1. <br /><br />Results showed that high-grade (grade 3) adverse events (AEs) occurred more frequently with AMILAZ (75%) than OSICT (64%), with an odds ratio (OR) of 1.68 (p=0.0022). Serious adverse events (SAEs) were also significantly higher in the AMILAZ group (49% vs. 38%; OR 1.56, p=0.0052), reflecting greater toxicity linked to dual EGFR–MET inhibition. Despite this increased toxicity, discontinuation rates due to AEs were comparable between groups (10% AMILAZ vs. 11% OSICT; OR 0.91, p=0.7064), indicating that the higher toxicity burden of AMILAZ did not translate into greater treatment cessation.<br /><br />These findings challenge conventional definitions of tolerability, revealing a "striking disconnect" where AMILAZ has a higher toxicity burden yet similar discontinuation rates compared to OSICT. This suggests that tolerability cannot be judged solely on incidence of severe AEs, but must also consider patient management and acceptance of side effects. The study highlights the need to weigh toxicity trade-offs critically alongside efficacy when selecting frontline therapies for EGFR-mutant NSCLC. In the absence of direct head-to-head trials focused on safety, toxicity profiles may become a decisive factor in clinical decision-making for this patient population.

Asset Subtitle

Blerina Resuli

Meta Tag

Speaker Blerina Resuli

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

EGFR-mutant non-small cell lung cancer

NSCLC

amivantamab

lazertinib

osimertinib

platinum-based chemotherapy

MARIPOSA trial

FLAURA2 trial

adverse events

tolerability