Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA
Recommended Citation
Felip E, Cho BC, Gutiérrez V, Alip A, Besse B, Lu S, Spira AI, Girard N, Califano R, Gadgeel SM, Yang JC, Yamamoto S, Azuma K, Kim YJ, Lee KH, Danchaivijitr P, Ferreira CG, Cheng Y, Sendur MAN, Chang GC, Wang CC, Prabhash K, Shinno Y, Stroyakovskiy D, Paz-Ares L, Rodriguez-Cid JR, Martin C, Campelo MRG, Hayashi H, Nguyen D, Tomasini P, Gottfried M, Dooms C, Passaro A, Schuler M, Gelatti ACZ, Owen S, Perdrizet K, Ou SI, Curtin JC, Zhang J, Gormley M, Sun T, Panchal A, Ennis M, Fennema E, Daksh M, Sethi S, Bauml JM, and Lee SH. Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA. Ann Oncol 2024.
Document Type
Article
Publication Date
9-1-2024
Publication Title
Annals of oncology
Abstract
BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups.
PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR).
RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004].
CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.
Medical Subject Headings
Humans; Carcinoma, Non-Small-Cell Lung; Acrylamides; ErbB Receptors; Lung Neoplasms; Mutation; Aniline Compounds; Male; Female; Middle Aged; Aged; Antineoplastic Combined Chemotherapy Protocols; Circulating Tumor DNA; Biomarkers, Tumor; Progression-Free Survival; Adult; Aged, 80 and over; Quinolines; Indoles; Pyrimidines
PubMed ID
38942080
ePublication
ePub ahead of print
Volume
35
Issue
9
First Page
805
Last Page
816
