Targeting HER2 Alterations with ADCs in NSCLC
Martin Dietrich, MD, PhD, examines the safety and efficacy of HER2-directed ADCs in NSCLC, emphasizing significant differences in response associated with HER alterations.
EP: 1.Exploring HER2 as a Pan Tumor Biomarker
EP: 2.HER2 in Breast Cancer: Shaping Treatment in Other Solid Tumors
EP: 3.Expert Insights on HER2-Directed ADCs in Breast Cancer
EP: 4.Targeting HER2 Alterations with ADCs in NSCLC
EP: 5.Landscape Surrounding HER2 ADCs in GI Cancers
EP: 6.Emerging Data for HER2 ADCs in Ovarian Cancer
EP: 7.HER2 ADCs in Endometrial Cancer: Shaping the Treatment Landscape
EP: 8.HER2 ADCs in Cervical Cancer: A Promising Therapeutic Frontier
EP: 9.Expert Insights on HER2 Testing in Gynecological Cancers
EP: 10.Future Perspectives on HER2 ADCs in Gynecological Cancer
Dr. Ritu Salani and Dr. Martin Dietrich discuss the use of antibody-drug conjugates (ADCs) in HER2-positive non-small cell lung cancer (NSCLC) and the challenges of retesting HER2 expression in breast cancer.
Regarding retesting HER2 expression in breast cancer, Dr. Dietrich acknowledges the importance of reconfirming receptors (estrogen, progesterone, and HER2) in the recurrent setting. However, he notes that trials used archival tissues, and obtaining fresh biopsies may not always be feasible. While fresh biopsies are preferable, he does not exclude patients if archival tissue shows HER2 positivity.
Moving on to NSCLC, Dr. Dietrich explains that HER2 in lung cancer is not as well understood as in breast cancer. The current approval of trastuzumab deruxtecan (T-DXd) in NSCLC is based on intracellular kinase domain mutations rather than amplification or overexpression. The DESTINY-Lung01 and DESTINY-Lung02 studies evaluated different alterations of HER2 and dosing schedules, with the 5.4 mg/kg dose eventually being approved.
HER2 in close connection to EGFR (HER1) has been challenging, as these subtypes do not respond well to immunotherapy. Off-label use of trastuzumab emtansine (T-DM1) showed modest responses (around 20%) and short durability. The DESTINY-Lung01 study demonstrated promising efficacy of T-DXd in HER2-mutant NSCLC, with a median progression-free survival of around 10 months and a more favorable toxicity profile at the lower dose.
T-DXd is currently the only approved therapy for HER2-mutant lung cancer and is a firmly established second-line standard of care. However, its role compared to standard therapies and the potential for combination with immunotherapy in the first-line setting remains to be determined. Ongoing confirmatory and combination studies will provide further insights.
Summary generated by Claude AI.
