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 - Institut Gustave Roussy
Journal Articles Annals of Oncology Year : 2024

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

E. Felip
  • Function : Author
B. C. Cho
  • Function : Author
V. Gutiérrez
  • Function : Author
A. Alip
  • Function : Author
B. Besse
S. Lu
  • Function : Author
A. I. Spira
  • Function : Author
R. Califano
  • Function : Author
S. M. Gadgeel
  • Function : Author
J. C.H. Yang
S. Yamamoto
K. Azuma
  • Function : Author
Y. J. Kim
K. H. Lee
  • Function : Author
P. Danchaivijitr
  • Function : Author
C. G. Ferreira
  • Function : Author
Y. Cheng
  • Function : Author
M. A.N. Sendur
  • Function : Author
G. C. Chang
  • Function : Author
C. C. Wang
  • Function : Author
K. Prabhash
  • Function : Author
Y. Shinno
  • Function : Author
D. Stroyakovskiy
  • Function : Author
L. Paz-Ares
  • Function : Author
J. R. Rodriguez-Cid
  • Function : Author
C. Martin
  • Function : Author
M. R.G. Campelo
  • Function : Author
H. Hayashi
  • Function : Author
D. Nguyen
M. Gottfried
  • Function : Author
C. Dooms
  • Function : Author
A. Passaro
M. Schuler
A. C.Z. Gelatti
  • Function : Author
S. Owen
  • Function : Author
K. Perdrizet
  • Function : Author
S. H.I. Ou
J. C. Curtin
  • Function : Author
J. Zhang
M. Gormley
  • Function : Author
M. Ennis
  • Function : Author
S. Sethi
  • Function : Author
J. M. Bauml
  • Function : Author
T. Sun
  • Function : Author
M. Daksh
  • Function : Author
A. Panchal
  • Function : Author
E. Fennema
  • Function : Author
S. H. Lee
  • Function : Author

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.
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hal-04724689 , version 1 (06-11-2024)

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E. Felip, B. C. Cho, V. Gutiérrez, A. Alip, B. Besse, et al.. 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. Annals of Oncology, 2024, 35 (9), pp.805-816. ⟨10.1016/j.annonc.2024.05.541⟩. ⟨hal-04724689⟩
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