Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: A Phase II Multicenter Study.

Autor:	Blakely CM; Department of Medicine, University of California, San Francisco, San Francisco, CA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA., Urisman A; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.; Department of Pathology, University of California, San Francisco, San Francisco, CA., Gubens MA; Department of Medicine, University of California, San Francisco, San Francisco, CA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA., Mulvey CK; Department of Medicine, University of California, San Francisco, San Francisco, CA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA., Allen GM; Department of Medicine, University of California, San Francisco, San Francisco, CA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA., Shiboski SC; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA., Rotow JK; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA., Chakrabarti T; Department of Medicine, University of California, San Francisco, San Francisco, CA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA., Kerr DL; Department of Medicine, University of California, San Francisco, San Francisco, CA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA., Aredo JV; Department of Medicine, University of California, San Francisco, San Francisco, CA., Bacaltos B; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA., Gee M; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA., Tan L; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA., Jones KD; Department of Pathology, University of California, San Francisco, San Francisco, CA., Devine WP; Department of Pathology, University of California, San Francisco, San Francisco, CA.; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA., Doebele RC; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO., Aisner DL; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO., Patil T; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO., Schenk EL; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO., Bivona TG; Department of Medicine, University of California, San Francisco, San Francisco, CA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.; Chan Zuckerberg Biohub, San Francisco, CA., Riess JW; Department of Medicine, University of California Davis, Sacramento, CA., Coleman M; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.; Department of Surgery, University of California, San Francisco, San Francisco, CA., Kratz JR; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.; Department of Surgery, University of California, San Francisco, San Francisco, CA., Jablons DM; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.; Department of Surgery, University of California, San Francisco, San Francisco, CA.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Sep 10; Vol. 42 (26), pp. 3105-3114. Date of Electronic Publication: 2024 Jul 19.
DOI:	10.1200/JCO.24.00071
Abstrakt:	Purpose: To assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR -mutated non-small cell lung cancer (NSCLC). Patients and Methods: This was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR -mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling. Results: A total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%). Conclusion: Treatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR -mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.
Databáze:	MEDLINE
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