Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC

Author(s): Byoung C. Cho, M.D., Ph.D. https://orcid.org/0000-0002-5562-270X, Shun Lu, M.D., Ph.D., Enriqueta Felip, M.D., Ph.D., Alexander I. Spira, M.D., Ph.D., Nicolas Girard, M.D., Ph.D., Jong-Seok Lee, M.D., Ph.D., Se-Hoon Lee, M.D., Ph.D., Yurii Ostapenko, M.D., Ph.D., Pongwut Danchaivijitr, M.D., Baogang Liu, M.D., Adlinda Alip, M.D., Ernesto Korbenfeld, M.D., Josiane Mourão Dias, M.D., Benjamin Besse, M.D., Ph.D., Ki-Hyeong Lee, M.D., Hailin Xiong, M.D., Soon-Hin How, M.D., Ying Cheng, M.D., Gee-Chen Chang, M.D., Ph.D., Hiroshige Yoshioka, M.D., Ph.D., James C.-H. Yang, M.D., Ph.D., Michael Thomas, M.D., Danny Nguyen, M.D., Sai-Hong I. Ou, M.D., Ph.D., Sanjay Mukhedkar, M.D., Kumar Prabhash, M.D., D.M., Manolo D’Arcangelo, M.D., Jorge Alatorre-Alexander, M.D., Juan C. Vázquez Limón, M.D., Sara Alves, M.D., Daniil Stroyakovskiy, M.D., Marina Peregudova, M.D., Ph.D., Mehmet A.N. Şendur, M.D., Ph.D., Ozan Yazici, M.D., Raffaele Califano, M.D., Vanesa Gutiérrez Calderón, M.D., Filippo de Marinis, M.D., Antonio Passaro, M.D., Ph.D. https://orcid.org/0000-0002-7575-3870, Sang-We Kim, M.D., Ph.D., Shirish M. Gadgeel, M.D., Ph.D., John Xie, Ph.D., Tao Sun, Ph.D., Melissa Martinez, M.S., Mariah Ennis, M.S., Elizabeth Fennema, M.A., Mahesh Daksh, Ph.D., Dawn Millington, M.S., Isabelle Leconte, Ph.D., Ryota Iwasawa, Ph.D., Patricia Lorenzini, M.S., Mahadi Baig, M.D., Sujay Shah, M.D., Joshua M. Bauml, M.D., S. Martin Shreeve, M.D., Ph.D., Seema Sethi, D.O., Roland E. Knoblauch, M.D., Ph.D., and Hidetoshi Hayashi, M.D., Ph.D. https://orcid.org/0000-0001-8787-5587, for the MARIPOSA Investigators*
Source: DOI: 10.1056/NEJMoa2403614

Dr. Maen Hussein's Thoughts

Another possible option for first line NSCLC EGFR mutated (non-exon 20) is Osimertinib (osi). Osi and chemotherapy had less brain metastases. And with Amivantamab and Lazertinib (EGFR inhibitor), the combination had better PFS and OS (HR0.8). Higher toxicity though with 10% discontinuation vs 3% for Osimertinib. This is interim analysis, toxicity was EGFR related mostly.

BACKGROUND

Amivantamab plus lazertinib (amivantamab–lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)–mutated advanced non–small-cell lung cancer (NSCLC).

METHODS

In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab–lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab–lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review.

RESULTS

Overall, 1074 patients underwent randomization (429 to amivantamab–lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab–lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab–lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab–lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab–lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab–lazertinib and 3% with osimertinib.

CONCLUSIONS

Amivantamab–lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.)

Author Affiliations

From the Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine (B.C.C.), Samsung Medical Center, Sungkyunkwan University School of Medicine (S.-H.L.), and the Lung Cancer Center, Asan Medical Center Cancer Institute (S.-W.K.), Seoul, the Department of Hematology–Oncology, Seoul National University Bundang Hospital, Seongnam (J.-S.L.), and the Medical Department, Chungbuk National University Hospital, Cheongju (K.-H.L.) — all in South Korea; the Department of Medical Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (S.L.), Harbin Medical University Cancer Hospital, Harbin (B.L.), the Department of Medical Oncology, Huizhou Municipal Central Hospital of Guangdong Province, Huizhou (H.X.), and Jilin Cancer Hospital, Changchun (Y.C.) — all in China; the Medical Oncology Service, Vall d’Hebron Barcelona Hospital Campus–Vall d’Hebron University Hospital, Barcelona (E. Felip), and the Medical Oncology Department, Hospital Regional Universitario de Málaga y Virgen de la Victoria, Institute of Biomedical Research of Malaga, Malaga (V.G.C.) — both in Spain; Virginia Cancer Specialists, Fairfax (A.I.S.); Institut Curie, Institut du Thorax Curie-Montsouris, Paris (N.G.), and Paris-Saclay University, Université de Versailles Saint-Quentin-en-Yvelines, Versailles (N.G.), and Paris-Saclay University and Institut Gustave Roussy, Villejuif (B.B.) — all in France; the National Cancer Institute, Kyiv, Ukraine (Y.O.); the Division of Medical Oncology, Department of Medicine, Siriraj Hospital Faculty of Medicine, Mahidol University Bangkok Noi Campus, Bangkok, Thailand (P.D.); the Clinical Oncology Unit, Faculty of Medicine, University of Malaya, Kuala Lumpur (A.A.), and the Department of Internal Medicine, Division of Respiratory Medicine, International Islamic University Malaysia Medical Specialist Center, Pahang (S.-H.H.) — both in Malaysia; British Hospital of Buenos Aires, Central British Hospital, Buenos Aires (E.K.); the Department of Medical Oncology, Barretos Cancer Hospital, São Paulo (J.M.D.); the School of Medicine and Institute of Medicine, Chung Shan Medical University, and the Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung (G.-C.C.), and the Department of Medical Oncology, National Taiwan University Cancer Center, Taipei (J.C.-H.Y.) — both in Taiwan; the Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata (H.Y.), and the Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka (H.H.) — both in Japan; the Department of Thoracic Oncology, Thoraxklinik, Heidelberg University Hospital, and the National Center for Tumor Diseases Heidelberg, German Center for Lung Research, Heidelberg, Germany (M.T.); City of Hope National Medical Center, Duarte (D.N.), Chao Family Comprehensive Cancer Center, University of California, Irvine, School of Medicine, Orange (S.-H.I.O.), and Janssen Research and Development, San Diego (E. Fennema, D.M., S.M.S.) — all in California; St. John of God Murdoch Hospital, Murdoch, WA, Australia (S.M.); the Department of Medical Oncology, Division of Adult Solid Tumor, Tata Memorial Center and Homi Bhabha National Institute, Mumbai, India (K.P.); the Local Health Unit Authority of Romagna, Ravenna Hospital and Department of Onco-Hematology, Santa Maria delle Croci Hospital of Ravenna, Ravenna (M. D’Arcangelo), and the Division of Thoracic Oncology, European Institute of Oncology IRCCS, Milan (F.M., A.P.) — both in Italy; Health Pharma Professional Research, Mexico City (J.A.-A.), Oncología Médica, Antiguo Hospital Civil de Guadalajara “Fray Antonio Alcalde,” Guadalajara, and Universidad de Guadalajara, Guadalajara (J.C.V.L.) — all in Mexico; Instituto Português de Oncologia do Porto, Porto, Portugal (S.A.); Moscow City Oncology Hospital No. 62 (D.S.) and the Medical Center in Kolomenskoe (M.P.) — both in Moscow; the Department of Medical Oncology, Ankara Bilkent City Hospital and Ankara Yıldırım Beyazıt University (M.A.N.Ş.), and the Department of Medical Oncology, Gazi University Faculty of Medicine (O.Y.) — both in Ankara, Turkey; the Department of Medical Oncology, Christie NHS Foundation Trust and Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom (R.C.); the Division of Hematology–Oncology, Henry Ford Cancer Institute, Henry Ford Health, Detroit (S.M.G.); Janssen Research and Development, Raritan, NJ (J.X., T.S., M.M., M. Daksh, M.B.); Janssen Research and Development, Spring House, PA (M.E., R.I., P.L., S. Shah, J.M.B., S. Sethi, R.E.K.); and Johnson and Johnson Clinical Innovation, Campus Basel, Allschwil, Switzerland (I.L.).

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