{
  "abstract": "INTRODUCTION: Amivantamab plus lazertinib is approved for first-line management of EGFR-mutated advanced NSCLC. In MARIPOSA, amivantamab-lazertinib significantly improved overall survival versus osimertinib (hazard ratio [HR]: 0.75; p = 0.005). We evaluated acquired resistance mechanisms and their impact on second-line progression-free survival (PFS) in MARIPOSA. METHODS: MARIPOSA (NCT04487080) assessed amivantamab-lazertinib versus osimertinib in previously untreated EGFR-mutated advanced NSCLC. Acquired resistance was assessed by Guardant360 next-generation sequencing of circulating tumor DNA from paired baseline and end-of-treatment plasma samples. Known resistance mechanisms included EGFR- orMET-dependent (e.g., C797S, MET amplification) and EGFR- or MET-independent (e.g., PIK3CA, RASorRAF, cell cycle, TP53orRB1 loss-of-function) resistance; absence of these detectable alterations constituted \"unknown\" resistance. Second-line PFS was defined as time from initiation of first subsequent therapy to investigator-assessed second progressive disease or death. RESULTS: MET amplifications (3.4% versus 13.1%; nominal p = 0.002) and secondary EGFR mutations (1.4% versus 7.6%; nominal p = 0.01) were significantly reduced with amivantamab-lazertinib versus osimertinib, without significant increases in other known resistance pathways. Longer treatment with amivantamab was associated with fewer acquired MET and EGFR mutations. Median second-line PFS was substantially prolonged in the amivantamab-lazertinib versus osimertinib arm (8.4 versus 5.3 mo; HR: 0.72; nominal p = 0.02) among participants who started a first subsequent therapy. Participants harboring unknown resistance at end of treatment had longer median second-line PFS versus known resistance (7.4 versus 4.6 mo; HR: 0.63; nominal p = 0.01). CONCLUSIONS: Amivantamab-lazertinib reduces common resistance mechanisms (e.g., EGFRorMET) versus osimertinib, suggesting that this regimen is changing the underlying biology of EGFR-mutant disease, contributing to both first- and second-line long-term efficacy outcomes.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "name": "Hidetoshi Hayashi"
    },
    {
      "name": "Byoung Chul Cho"
    },
    {
      "name": "David R. Spigel"
    },
    {
      "name": "Nicolas Girard"
    },
    {
      "name": "Se-Hoon Lee"
    },
    {
      "name": "Shun Lu"
    },
    {
      "name": "Sanjay Popat"
    },
    {
      "name": "James Chih-Hsin Yang"
    },
    {
      "name": "Antonio Passaro"
    },
    {
      "name": "Clarissa Baldotto"
    },
    {
      "name": "Maya Gottfried"
    },
    {
      "name": "Josiane Mourão Dias"
    },
    {
      "name": "Ana Caroline Zimmer Gelatti"
    },
    {
      "name": "Bo Wang"
    },
    {
      "name": "Julian Kam"
    },
    {
      "name": "Seema Sethi"
    },
    {
      "name": "Sujay Shah"
    },
    {
      "name": "Medha Kamat"
    },
    {
      "name": "Jiarui Zhang"
    },
    {
      "name": "Joshua C. Curtin"
    },
    {
      "name": "William N. William"
    },
    {
      "name": "Benjamin Besse"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f2chava3wafkr.bib",
  "cited_by": 5,
  "doi": "10.1016/j.jtho.2026.103894",
  "fulltext_url": null,
  "id": "f2chava3wafkr",
  "issns": [
    "1556-0864",
    "1556-1380"
  ],
  "landing_url": "https://hal.science/hal-05851600v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2740|Lung Cancer Treatments and Mutations"
    ]
  ],
  "openalex": "W7159608942",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "42061572",
  "published": "2026-11-04",
  "publisher": "Lippincott, Williams & Wilkins",
  "ris": "https://research.draconitic.com/paper/f2chava3wafkr.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:20:53Z",
      "native_id": "hal-05851600",
      "source": "hal",
      "url": "https://hal.science/hal-05851600v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "journal-openalex:2730|Lung Cancer Research Studies",
      "subfield": "oncology"
    }
  ],
  "title": "Long-Term Impact of First-Line Amivantamab Plus Lazertinib Versus Osimertinib on Mechanisms of Acquired Resistance in MARIPOSA: A Brief Report",
  "title_text": "Long-Term Impact of First-Line Amivantamab Plus Lazertinib Versus Osimertinib on Mechanisms of Acquired Resistance in MARIPOSA: A Brief Report",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:13Z",
  "url": "https://research.draconitic.com/paper/f2chava3wafkr",
  "venue": "Journal of Thoracic Oncology",
  "versions": []
}