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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

Felip E 1 , Cho BC 2 , Gutiérrez V 3 , Alip A 4 , Besse B 5 , Lu S 6 Show all authors , Spira AI 7 , Girard N 8 , Califano R 9 , Gadgeel SM 10 , Yang JC 11 , Yamamoto S 12 , Azuma K 13 , Kim YJ 14 , Lee KH 15 , Danchaivijitr P 16 , Ferreira CG 17 , Cheng Y 18 , Sendur MAN 19 , Chang GC 20 , Wang CC 21 , Prabhash K 22 , Shinno Y 23 , Stroyakovskiy D 24 , Paz-Ares L 25 , Rodriguez-Cid JR 26 , Martin C 27 , Campelo MRG 28 , Hayashi H 29 , Nguyen D 30 , Tomasini P 31 , Gottfried M 32 , Dooms C 33 , Passaro A 34 , Schuler M 35 , Gelatti ACZ 36 , Owen S 37 , Perdrizet K 38 , Ou SI 39 , Curtin JC 40 , Zhang J 40 , Gormley M 40 , Sun T 41 , Panchal A 42 , Ennis M 40 , Fennema E 43 , Daksh M 41 , Sethi S 40 , Bauml JM 40 , Lee SH 44

Affiliations 

  • 1 Medical Oncology Service, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Universitat Autonoma de Barcelona, Barcelona, Spain. Electronic address: [email protected]
  • 2 Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
  • 3 Medical Oncology Department, Hospital Regional Universitario de Málaga y Virgen de la Victoria, IBIMA, Málaga, Spain
  • 4 Clinical Oncology Unit, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 5 Paris-Saclay University, Gustave Roussy, Villejuif, France
  • 6 Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • 7 Virginia Cancer Specialists, Fairfax, VA, USA
  • 8 Institut du Thorax Curie-Montsouris, Paris, France; Paris Saclay University, Université de Versailles Saint-Quentin-en-Yvelines, Versailles, France
  • 9 Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, The University of Manchester, Manchester, UK
  • 10 Department of Internal Medicine, Henry Ford Cancer Institute, Detroit, MI, USA
  • 11 National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan
  • 12 Ehime University Hospital, Toon, Ehime
  • 13 Kurume University School of Medicine, Kurume, Japan
  • 14 Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
  • 15 Medical Department, Chungbuk National University Hospital, Cheongju, Republic of Korea
  • 16 Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
  • 17 Oncoclinicas&CO/MedSir, Rio de Janeiro, Brazil
  • 18 Jilin Cancer Hospital, Changchun, China
  • 19 Department of Medical Oncology, Ankara Bilkent City Hospital and Ankara Yıldırım Beyazıt University, Ankara, Turkey
  • 20 School of Medicine and Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
  • 21 Division of Pulmonary & Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
  • 22 Department of Medical Oncology, Tata Memorial Centre, HBNI, Mumbai, India
  • 23 Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan
  • 24 Healthcare Department, Moscow City Oncology Hospital No. 62, Moscow, Russia
  • 25 CNIO-H120 Lung Cancer Unit, University Hospital 12 de Octubre, Universidad Complutense de Madrid and CIBERONC, Madrid, Spain
  • 26 Médica Sur, Ciudad de México, CDMX, Mexico
  • 27 Thoracic Oncology Unit and Clinical Research Unit, Department of Medical Oncology, Alexander Fleming Cancer Institute, Buenos Aires, Argentina
  • 28 Medical Oncology, Hospital Universitario A Coruña, A Coruña, Spain
  • 29 Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan
  • 30 City of Hope National Medical Center, Duarte, CA, USA
  • 31 Aix Marseille University, APHM, INSERM, NCRS, CRCM, Hôpital de la Timone, Multidisciplinary Oncology & Therapeutic Innovations Department, Marseille, France
  • 32 Meir Medical Center, Kfar-Sava, Israel
  • 33 Respiratory Oncology Unit, University Hospitals Leuven, Leuven, Belgium
  • 34 Division of Thoracic Oncology, European Institute of Oncology IRCCS, Milan, Italy
  • 35 West German Cancer Center, Department of Medical Oncology, University Hospital Essen, Essen, Germany
  • 36 Uniao Brasileira de Educaçao e Assistencia-Hospital Sao Lucas da PUCRS, Porto Alegre-RS, Brazil
  • 37 Department of Oncology, McGill University, Montréal, QC, Canada
  • 38 William Osler Health System, Brampton, ON, Canada
  • 39 Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA, USA
  • 40 Janssen Research & Development, Spring House, PA, USA
  • 41 Janssen Research & Development, Raritan, NJ, USA
  • 42 Janssen Research & Development, High Wycombe, UK
  • 43 Janssen Research & Development, San Diego, CA, USA
  • 44 Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Ann Oncol, 2024 Sep;35(9):805-816.
PMID: 38942080 DOI: 10.1016/j.annonc.2024.05.541

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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