POSing the question: MARIPOSA-2, do the ends justify the means?

Osimertinib monotherapy is the preferred first-line treatment for patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC), although this may soon change with the recent FLAURA2 and MARIPOSA results. 1 Soria J.-C. Ohe Y. Vansteenkiste J. et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2017; 378: 113-125 Crossref PubMed Scopus (3164) Google Scholar , 2 Ramalingam S.S. Vansteenkiste J. Planchard D. et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2019; 382: 41-50 Crossref PubMed Scopus (1434) Google Scholar , 3 Planchard D. Jänne P.A. Cheng Y. et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. New Engl J Med. 2023; 389: 1935-1948 Crossref Scopus (1) Google Scholar Despite initial efficacy, most patients develop resistance to osimertinib, at which point platinum-based chemotherapy remains the standard of care. When possible, adapting treatment based on mechanisms of resistance identified using tissue-based genomic testing improves survival. 4 Choudhury N.J. Marra A. Sui J.S.Y. et al. Molecular biomarkers of disease outcomes and mechanisms of acquired resistance to first-line osimertinib in advanced EGFR-mutant lung cancers. J Thorac Oncol. 2023; 18: 463-475 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar Despite this, there are no approved targeted treatments in the post-osimertinib setting and enthusiasm to supplant or improve on chemotherapy is high. Amivantamab, an EGFR-MET bispecific antibody, in combination with lazertinib, a third-generation EGFR tyrosine kinase inhibitor, has generated excitement after the phase I CHRYSALIS trial demonstrated an overall response rate (ORR) of 36% and median progression-free survival (PFS) of 4.9 months in patients with EGFR NSCLC who had progressed on third-generation tyrosine kinase inhibitor. 5 Cho B.C. Kim D.-W. Spira A.I. et al. Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial. Nat Med. 2023; 29: 2577-2585 Crossref Scopus (2) Google Scholar Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 studyAnnals of OncologyPreviewAmivantamab plus carboplatin–pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. Full-Text PDF Open Access