Dr Tolaney on Ongoing Clinical Trials in Early-Stage HER2+ 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 ongoing clinical trials investigating novel approaches and combination therapies for patients with early-stage HER2-positive breast cancer.

During a presentation on the treatment of early-stage HER2-positive breast cancer given at the 23rd Annual International Congress on the Future of Breast Cancer® East, Tolaney underscored how ongoing trials investigating the sequencing of antibody-drug conjugates (ADCs) and adding HER2-directed therapies to existing treatment regimens could help inform and shape treatment strategies for this patient population in the future.

Tolaney highlights the phase 3 CompassHER2 RD trial (NCT04457596), which is an ongoing prospective, multicenter study investigating the addition of tucatinib (Tukysa) to ado-trastuzumab emtansine (T-DM1; Kadcyla) in patients who presented with T1 to T4, N0 to N3, HER2-positive breast cancer and had residual disease following surgery. In this setting, 14 doses of T-DM1 has been the standard of care, Tolaney explains. In CompassHER2 RD, patients are being randomly assigned to receive T-DM1 plus placebo or T-DM1 plus tucatinib for up to 14 cycles or until disease progression or unacceptable toxicity. Tolaney notes that tucatinib, a HER2-directed TKI, has demonstrated the ability to penetrate the blood-brain barrier, highlighting its potential to prevent recurrent metastases in the brain.

Tolaney also mentions fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) as another agent being investigated in the early-stage setting after replacing T-DM1 as the standard-of-care in the second-line setting for patients with metastatic HER2-positive breast cancer. Although T-DXd outperformed T-DM1 in the metastatic setting, clinical trials will determine if it can improve outcomes in the adjuvant setting, Tolaney says.

The phase 3 DESTINY-Breast05 study (NCT04622319) is assessing T-DXd vs T-DM1 in patients with HER2-positive breast cancer who have residual invasive disease in the breast or axillary lymph nodes with a higher risk of recurrence. These studies highlight the effort to bring new HER2-directed therapies to the early-stage setting, Tolaney concludes.