Felip, E. and Cho, B. C. and Gutierrez, V and Alip, A. and Besse, B. and Lu, S. and Spira, A. I. and Girard, N. and Califano, R. and Gadgeel, S. M. and Yang, J. C-H. and Yamamoto, S. and Azuma, K. and Kim, Y. J. and Lee, K. -H. and Danchaivijitr, P. and Ferreira, C. G. and Cheng, Y. and Sendur, M. A. N. and Chang, G. -C. and Wang, C. -C. and Prabhash, K. and Shinno, Y. and Stroyakovskiy, D. and Paz-Ares, L. and Rodriguez-Cid, J. R. and Martin, C. and Campelo, M. R. G. and Hayashi, H. and Nguyen, D. and Tomasini, P. and Gottfried, M. and Dooms, C. and Passaro, A. and Schuler, M. and Gelatti, A. C. Z. and Owen, S. and Perdrizet, K. and Ou, S. -H. I. and Curtin, J. C. and Zhang, J. and Gormley, M. and Sun, T. and Panchal, A. and Ennis, M. and Fennema, E. and Bauml, J. M. and Daksh, M. and Sethi, S. and Lee, S. -H. (2024) 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. Annals of Oncology, 35 (9). pp. 805-816. ISSN 0923-7534, DOI https://doi.org/10.1016/j.annonc.2024.05.541.
Full text not available from this repository.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.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | amivantamab; lazertinib; NSCLC; biomarkers; ctDNA; TP53 |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 14 Apr 2025 06:37 |
| Last Modified: | 14 Apr 2025 06:37 |
| URI: | http://eprints.um.edu.my/id/eprint/46596 |
Actions (login required)
 |
View Item |
