Dr Nanda on the Evolution of Treatment For HER2-Low Breast Cancer

Rita Nanda, MD, associate professor, medicine, director, Breast Oncology Program, University of Chicago, UChicago Medicine, discusses the evolution of treatment options for patients with HER2-low breast cancer.

Nanda shares that the FDA approval of fam-trastuzumab deruxtecan-nxki(Enhertu) for patients with unresectable or metastatic HER2-low disease represents a significant milestone in oncology, Nanda begins. This regulatory decision has provided patients with HER2-low disease with a chance for prolonged progression-free survival and overall survival, she states. Looking ahead, a critical question arises regarding patients with HER2 levels falling below the conventional threshold, Nanda explains. The ongoing phase 3DESTINY-Breast06 trial (NCT04494425) aims to address this query by investigating trastuzumab deruxtecan's efficacy in patients with HER2-low disease, including those with HER2 levels greater than 0 but less than 1+ she adds.

Moreover, the challenge of optimizing treatment sequencing emerges, particularly for patients eligible for multiple antibody-drug conjugates (ADCs), Nanda continues. Patients with triple-negative breast cancer and those with hormone receptor (HR)–positive disease are candidates for sacituzumab govitecan-hziy (Trodelvy), and patient eligibility for this agent often overlaps with that for HER2-targeting ADCs, Nanda says. The critical inquiry revolves around determining the most effective sequence for TROP2-targeted ADCs and HER2-targeted ADCs in patients with HER2-low disease, according to Nanda. Although randomized data from ongoing trials are eagerly anticipated, data from current registry trials indicate that sequential administration of ADCs may not yield the anticipated efficacy for the second ADC, she elucidates.

Moving forward, there remains a pressing need to further comprehend the optimal use of ADCs in patients eligible for multiple therapies, Nanda continues. This necessitates ongoing research efforts and a forward-looking approach to elucidate the most effective treatment sequencing strategies, she adds. As oncologists navigate this evolution, the goal is to optimize therapeutic outcomes and improve the standard of care for patients with HER2-low disease, ensuring each patient receives the most beneficial treatment regimen tailored to their specific disease characteristics and treatment history, Nanda concludes.