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

作者：Enriqueta Felip, Byoung Chul Cho, V. Gutiérrez, Adlinda Alip, Benjamin Besse, Shaolin Lü, Alexander I. Spira, N. Girard, Raffaele Califano, S.M. Gadgeel, James Chih‐Hsin Yang, Sadamu YAMAMOTO, K. Azuma, Yu Jung Kim, K.-H. Lee, Pongwut Danchaivijitr, C.G. Ferreira, Yun Cheng, Mehmet Alı Nahıt Şendur, G.-C. Chang, C.-C. Wang, K. Prabhash, Y. Shinno, Daniil Stroyakovskiy, L. Paz-Ares, Jerónimo Rafael Rodríguez‐Cid, Claire Martin, M.R. García Campelo, H. Hayashi, Danny Nguyen, P. Tomasini, Maya Gottfried, Christophe Dooms, Antonio Passaro, Martin Schüler, A.C.Z. Gelatti, Scott Owen, K. Perdrizet, S.-H.I. Ou, J.C. Curtin, J. Zhang, Michael Gormley, Tingting Sun, Amey C Panchal, Marguerite Ennis, E. Fennema, Mahesh Daksh, Seema Sethi, J.M. Bauml, S.-H. Lee · 发表于：Annals of Oncology · 年份：2024 · DOI：10.1016/j.annonc.2024.05.541 · 被引用次数：87 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics、Melanoma and MAPK Pathways

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-...