Opinion
Video
EGFR-Mutated NSCLC: Treatment Options Following Progression on Osimertinib
Author(s):
Ticiana Leal, MD, gives a comprehensive overview of treatment options for patients with EGFR-mutated NSCLC who progress on osimertinib therapy.
This is a synopsis of an Insights series featuring Ticiana Leal, MD, of Winship Cancer Institute of Emory University, and Sandip P. Patel, MD, of UC San Diego Health Moores Cancer Center.
Associate Professor and Director of the Thoracic Medical Oncology Program at the Winship Cancer Institute of Emory University Ticiana Leal, MD and Professor of Medical Oncology at the University of California, San Diego Sandip P. Patel, MD discussed treatment options after progression on the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib for EGFR mutated non–small cell lung cancer (NSCLC).
Dr. Leal emphasized interrogating mechanisms of resistance through repeat biopsy to assess for small cell transformation, which profoundly impacts prognosis and treatment. Without contraindications, standard of care is transitioning to platinum plus pemetrexed chemotherapy. Continuing osimertinib is also commonly done, especially with central nervous system metastases, although optimal combinations lack definitive data. Addition of the vascular endothelial growth factor inhibitor bevacizumab to chemotherapy is also an option with proven efficacy in non-squamous NSCLC.
Regarding immunotherapy, Dr. Leal has been underwhelmed by data in the EGFR TKI refractory setting. Monotherapy PD-L1 inhibition is inferior to docetaxel chemotherapy per subset analyses. The only potential signal was an exploratory analysis from the IMpower150 trial showing improved overall survival adding atezolizumab to carboplatin/paclitaxel/bevacizumab in EGFR TKI pretreated patients, but these results require validation. Most recently, the KEYNOTE-189 regimen failed to improve outcomes in this population. Given current data, Dr. Leal favors exploring antibody-drug conjugates over immunotherapy for TKI resistant EGFR mutated NSCLC.
Dr. Patel concurred that more research is imperative to identify better treatment options after osimertinib failure, highlighting antibody-drug conjugates targeting HER3 as one emerging approach warranting ongoing investigation.
*Video synopsis is AI-generated and reviewed by OncLive editorial staff.
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