%0 Journal Article
%T 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.
%A Felip E
%A Cho BC
%A Gutiérrez V
%A Alip A
%A Besse B
%A Lu S
%A Spira AI
%A Girard N
%A Califano R
%A Gadgeel SM
%A Yang JC
%A Yamamoto S
%A Azuma K
%A Kim YJ
%A Lee KH
%A Danchaivijitr P
%A Ferreira CG
%A Cheng Y
%A Sendur MAN
%A Chang GC
%A Wang CC
%A Prabhash K
%A Shinno Y
%A Stroyakovskiy D
%A Paz-Ares L
%A Rodriguez-Cid JR
%A Martin C
%A Campelo MRG
%A Hayashi H
%A Nguyen D
%A Tomasini P
%A Gottfried M
%A Dooms C
%A Passaro A
%A Schuler M
%A Gelatti ACZ
%A Owen S
%A Perdrizet K
%A Ou SI
%A Curtin JC
%A Zhang J
%A Gormley M
%A Sun T
%A Panchal A
%A Ennis M
%A Fennema E
%A Daksh M
%A Sethi S
%A Bauml JM
%A Lee SH
%J Ann Oncol
%V 0
%N 0
%D 2024 Jun 26
%M 38942080
%F 51.769
%R 10.1016/j.annonc.2024.05.541
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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).<BR><B>RESULTS: </B>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].<BR><B>CONCLUSIONS: </B>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.