Dr Tolaney on the Real-World Efficacy of T-DXd in HER2+ or HER2-Low Breast Cancer

Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women's Cancers, associate director, Susan F. Smith Center for Women's Cancers, senior physician, Dana-Farber Cancer Institute, associate professor of Medicine, Harvard Medical School, discusses the real-world efficacy of fam-trastuzumab deruxtecan (T-DXd; Enhertu) in patients with HER2-positive or HER2-low metastatic breast cancer, including patients who experienced changes in HER2 status during the treatment course.

The RELIEVE study collected data from patients in the United States with advanced breast cancer treated with T-DXd between July 2017 and February 2022 at Dana-Farber Cancer Institute and between March 2020 and April 2022 at Duke Cancer Center, Tolaney begins. Key study end points included time to next treatment (TTNT), progression-free survival (PFS), overall survival (OS), toxicities, and TTNT with post-T-DXd regimens.

Findings presented at the 2023 San Antonio Breast Cancer Symposium showed that T-DXd significantly prolonged time-to-next treatment in this population, producing the longest TTNT in patients with HER2-positive disease or with stable HER2-low disease in the primary and metastatic setting.

At a median 10.4 months of follow-up (P < .001), the median TTNT after T-DXd was 10.4 months, 7.6 months, and 3.7 months in 191 real-world patients with HER2-positive, HER2-low, and HER2-0 status, respectively, Tolaney reports.

The study also explored whether dynamic HER2 status impacted outcomes with T-DXd. Patients consistently categorized as HER2-low both in the primary and metastatic settings experienced more prolonged outcomes vs those with changing status, Tolaney states. Patients experiencing a change in HER2 expression from HER2-low to HER2-0 had a shorter median TTNT of 3.0 months vs 5.6 months for those transitioning from HER2-0 to HER2-low, and 9.4 months for stable HER2-low expression (P = .006), Tolaney adds.

These variations indicate that changing HER2 status did influence patient benefit from T-DXd, with a shift from HER2-low to HER2-0 correlating with a shorter response. Given the dynamic nature of HER2 status, this finding reflects the importance of understanding how such fluctuations impact efficacy, Tolaney concludes.