Current Treatment Landscape for EGFR-Mutated NSCLC

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EP: 1.Current Treatment Landscape for EGFR-Mutated NSCLC

EP: 2.Treatment Options for EGFR-Mutated NSCLC Following Progression

EP: 3.EGFR-Mutated NSCLC: Treatment Options Following Progression on Osimertinib

EP: 4.Treatments and Unmet Needs for EGFR-Mutated NSCLC

EP: 5.The Role of HER3 in Non–Small Cell Lung Cancer

EP: 6.HERTHENA-Lung01: Patritumab Deruxtecan in Advanced EGFR-Mutated NSCLC

EP: 7.NSCLC: Safety Outcomes from HERTHENA-Lung01

EP: 8.Role of HER3-DXd in Advanced NSCLC Treatment Landscape

EP: 9.Ongoing Research on HER3-DXd in NSCLC

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 targeting HER3 in patients with advanced non–small cell lung cancer (NSCLC).

Dr. Leal noted current guidelines recommend treatment with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) like osimertinib in the first-line setting for advanced or metastatic EGFR mutated NSCLC based on the FLAURA trial. Osimertinib led to improved outcomes and favorable safety compared to first-generation EGFR TKIs. However, resistance develops through mechanisms like the C797S mutation, bypass tracks, and small cell transformation. The FLAURA2 trial studied osimertinib plus carboplatin/pemetrexed in the frontline setting, showing improved progression-free survival but increased side effects. Recently, the ADAURA trial demonstrated improved outcomes with adjuvant osimertinib after resection in early-stage EGFR mutated NSCLC.

Key unmet needs include comprehensive biomarker testing access for all NSCLC patients and determining if osimertinib combinations have a role for subsets of patients. Further study is needed in specific EGFR mutated populations like those with brain metastases and L858R mutations. Understanding resistance mechanisms like small cell transformation is critical.

Dr. Patel discussed apparent HER3 upregulation seen after progression on osimertinib. The anti-HER3 antibody-drug conjugates patritumab deruxtecan (U3-1402) and HER3-DXd are being studied to target this. Early results from the phase 1 HERTHENA-Lung01 and phase 2 HERTHENA-Lung02 trials studying patritumab deruxtecan showed promising activity. Ongoing work is investigating optimal positioning for these HER3 targeting strategies.

Dr. Leal agreed studying ways to overcome resistance is key. She highlighted interest in studying patritumab deruxtecan plus osimertinib upfront in EGFR mutated NSCLC with brain metastases based on preclinical data. Both speakers emphasized the importance of continued research and clinical trials to provide more treatment options for patients with EGFR mutated NSCLC.

*Video synopsis is AI-generated and reviewed by OncLive editorial staff.