In the past 2 years, substantial improvements have been made in the management of advanced-stage EGFR-mutant non-small-cell lung cancer. Recent studies have suggested added benefit from the combination of third-generation tyrosine-kinase inhibitors with either chemotherapy or a bispecific antibody targeting EGFR and MET. Herein, we summarize these advances and their implications for clinical practice.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Sharma, S. V., Bell, D. W., Settleman, J. & Haber, D. A. Epidermal growth factor receptor mutations in lung cancer. Nat. Rev. Cancer 7, 169–181 (2007).
Morgillo, F., Della Corte, C. M., Fasano, M. & Ciardiello, F. Mechanisms of resistance to EGFR-targeted drugs: lung cancer. ESMO Open 1, e000060 (2016).
Cross, D. A. et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 4, 1046–1061 (2014).
Ramalingam, S. S. et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N. Engl. J. Med. 382, 41–50 (2020).
Nieva, J., Reckamp, K. L., Potter, D., Taylor, A. & Sun, P. Retrospective analysis of real-world management of EGFR-mutated advanced NSCLC, after first-line EGFR-TKI treatment: US treatment patterns, attrition, and survival data. Drugs Real World Outcomes 9, 333–345 (2022).
Cho, B. C. et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2403614 (2024).
Felip, E. et al. 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. Ann. Oncol. https://doi.org/10.1016/j.annonc.2024.05.541 (2024).
Planchard, D. et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N. Engl. J. Med. 389, 1935–1948 (2023).
Passaro, A. et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann. Oncol. 35, 77–90 (2024).
Passaro, A., Jänne, P. A., Mok, T. & Peters, S. Overcoming therapy resistance in EGFR-mutant lung cancer. Nat. Cancer 2, 377–391 (2021).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
S.S.R. has received institutional research grants for clinical trials support from Amgen, AstraZeneca, Bristol Myers Squibb, Merck and Pfizer. F.A.-L. declares no competing interests.
Rights and permissions
About this article
Cite this article
Ardeshir-Larijani, F., Ramalingam, S.S. The MARIPOSA trials — implications for the treatment of EGFR-mutant NSCLC. Nat Rev Clin Oncol (2024). https://doi.org/10.1038/s41571-024-00938-3
Published:
DOI: https://doi.org/10.1038/s41571-024-00938-3
