Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study
Year: 2023
Type: article
Study design: Observational Study
Abstract: Introduction EGFR mutations drive a subset of NSCLC. Patients harboring the common EGFR mutations, deletion of exon 19 and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. Nevertheless, the effect of osimertinib on NSCLC with atypical EGFR mutations is not well described. This multicenter retrospective study evaluates the efficacy of osimertinib among patients with NSCLC harboring atypical EGFR mutations. Methods Patients with metastatic NSCLC treated with osimertinib, harboring at least one atypical EGFR mutation, excluding concurrent deletion of exon 19, L858R, or T790M mutations, from six U.S. academic cancer centers were included. Baseline clinical characteristics were collected. The primary end point was the time to treatment discontinuation (TTD) of osimertinib. Objective response rate by the Response Evaluation Criteria in Solid Tumors version 1.1 was also assessed. Results A total of 50 patients with NSCLC with uncommon EGFR mutations were identified. The most frequent EGFR mutations were L861Q (40%, n = 18), G719X (28%, n = 14), and exon 20 insertion (14%, n = 7). The median TTD of osimertinib was 9.7 months (95% confidence interval [CI]: 6.5–12.9 mo) overall and 10.7 months (95% CI: 3.2–18.1 mo) in the first-line setting (n = 20). The objective response rate was 31.7% (95% CI: 18.1%–48.1%) overall and 41.2% (95% CI: 18.4%–67.1%) in the first-line setting. The median TTD varied among patients with L861Q (17.2 mo), G719X (7.8 mo), and exon 20 insertion (1.5 mo) mutations. Conclusions Osimertinib has activity in patients with NSCLC harboring atypical EGFR mutations. Osimertinib activity differs by the type of atypical EGFR -activating mutation.
Authors: Jingran Ji, Jacqueline V. Aredo, Andrew Piper-Vallillo, Laura Huppert, Julia K. Rotow, Hatim Husain, Susan Stewart, Rosemary Cobb, Heather A. Wakelee, Collin M. Blakely, Melisa L. Wong, Matthew A. Gubens, Mohammad H. Madani, Subba R. Digumarthy, Caroline McCoach, Zofia Piotrowska, Joel W. Neal, Jonathan W. Riess
Institutions: City Of Hope National Medical Center, City of Hope, UC Davis Comprehensive Cancer Center, Stanford Cancer Institute, Stanford University, Massachusetts General Hospital, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, Dana-Farber Cancer Institute, University of California San Diego, Moores Cancer Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,000
Funders: Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, International Association for the Study of Lung Cancer, American College of Radiology Imaging Network, Celgene, Helsinn, Regeneron Pharmaceuticals, Jazz Pharmaceuticals, Clovis Oncology, BeiGene, ECOG-ACRIN Cancer Research Group, Cardinal Health, Revolution Medicines, Lunit, Seagen, National Institutes of Health, Genentech, EMD Serono, Sanofi Genzyme, Foundation Medicine, National Cancer Institute, Janssen Biotech, Daiichi Sankyo Europe
OpenAlex ID: W4313856913