Dr. Tolaney on Sequencing Strategies in Metastatic HER2+ Breast Cancer

Sara M. Tolaney, MD, MPH, associate director of the Susan F. Smith’s Center for Women’s Cancers, director of Clinical Trials, Breast Oncology, senior physician at Dana-Farber Cancer Institute, and assistant professor of medicine at Harvard Medical School, discusses sequencing strategies in metastatic HER2-positive breast cancer.

On December 20 2019, the FDA granted an accelerated approval to fam-trastuzumab deruxtecan-nxki (DS-8201; Enhertu) for patients with unresectable or metastatic HER2-positive breast cancer who have received at least 2 prior anti—HER2-based regimens in the metastatic setting.

More recently, on April 17 2020, the FDA approved tucatinib (Tukysa) in combination with trastuzumab (Herceptin) and capecitabine (Xeloda) for the same patient population who have received at least 1 prior anti—HER2-based therapy in the metastatic setting. The approval, which is based on data from the phase 2 HER2CLIMB trial, is also indicated for patients with brain metastases.

Both regimens can be considered for patients who received prior docetaxel, trastuzumab, and pertuzumab (Perjeta) in the frontline setting and ado-trastuzumab emtansine (T-DM1; Kadcyla) in the second-line setting, says Tolaney.

Patients with brain metastases should receive the tucatinib-based regimen, explains Tolaney. Unlike the phase 2 HER2CLIMB trial which included patients with progressive or untreated brain metastases, the phase 2 DESTINY-Breast01 trial with trastuzumab deruxtecan limited enrollment to a small number of patients with stable and treated brain metastases, explains Tolaney.

If patients progress on either third-line option, the alternative regimen can be implemented as a fourth-line therapy, concludes Tolaney.