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.
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
Journal Volume
35
Journal Issue
9
Start Page
805
End Page
816
ISSN
1569-8041
Date Issued
2024-09
Author(s)
Felip, E
Cho, B C
Gutiérrez, V
Alip, A
Besse, B
Lu, S
Spira, A I
Girard, N
Califano, R
Gadgeel, S M
Yamamoto, S
Azuma, K
Kim, Y J
Lee, K-H
Danchaivijitr, P
Ferreira, C G
Cheng, Y
Sendur, M A N
Chang, G-C
WANG CC
Prabhash, K
Shinno, Y
Stroyakovskiy, D
Paz-Ares, L
Rodriguez-Cid, J R
Martin, C
Campelo, M R G
Hayashi, H
Nguyen, D
Tomasini, P
Gottfried, M
Dooms, C
Passaro, A
Schuler, M
Gelatti, A C Z
Owen, S
Perdrizet, K
Ou, S-H I
Curtin, J C
Zhang, J
Gormley, M
Sun, T
Panchal, A
Ennis, M
Fennema, E
Daksh, M
Sethi, S
Bauml, J M
Lee, S-H
Abstract
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.
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).
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].
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.
Subjects
NSCLC
TP53
amivantamab
biomarkers
ctDNA
lazertinib
SDGs
Type
journal article