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

• Published in: Journal of clinical oncology Vol. 42; no. 26; pp. 3105 - 3114
• Main Authors: Blakely, Collin M, Urisman, Anatoly, Gubens, Matthew A, Mulvey, Claire K, Allen, Greg M, Shiboski, Stephen C, Rotow, Julia K, Chakrabarti, Turja, Kerr, D Lucas, Aredo, Jacqueline V, Bacaltos, Bianca, Gee, Megan, Tan, Lisa, Jones, Kirk D, Devine, W Patrick, Doebele, Robert C, Aisner, Dara L, Patil, Tejas, Schenk, Erin L, Bivona, Trever G, Riess, Jonathan W, Coleman, Melissa, Kratz, Johannes R, Jablons, David M
• Format: Journal Article
• Language: English
• Published: United States 10-09-2024
• Subjects: Acrylamides - therapeutic use; Adult; Aged; Aniline Compounds - adverse effects; Aniline Compounds - therapeutic use; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; ErbB Receptors - genetics; Female; Humans; Indoles; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Middle Aged; Mutation; Neoadjuvant Therapy; Neoplasm Staging; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrimidines
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.24.00071

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
-mutated non-small cell lung cancer (NSCLC).
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)
-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.
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
(42%) and
(21%).
Treatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7)
-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.