Sara M. Tolaney, MD, MPH, associate director of the Susan F. Smith 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 the unmet need with regard to effectively preventing central nervous system (CNS) recurrence in HER2-positive breast cancer.

In the early disease setting, the field continues to do a better job of curing patients with HER2-positive disease, with the addition of pertuzumab (Perjeta), T-DM1 (ado-trastuzumab emtansine; Kadcyla), and sometimes neratinib (Nerlyx), says Tolaney. However, despite these advances, some patients still recur after these treatments. Interestingly, in the phase 3 KATHERINE study, 5% of disease-free survival events observed were CNS recurrences, notes Tolaney. In fact, no benefit with T-DM1 over trastuzumab was observed with regard to preventing those recurrences.

The field is left with the unmet need of trying to decrease CNS recurrences, and it begs the question of how that need can be addressed. Some have hypothesized that using a TKI, such as tucatinib (Tukysa), could potentially address this need, based on the activity observed with the agent in the metastatic setting, says Tolaney.

To this end, an arm in the COMPASS trial is enrolling patients with residual disease after preoperative HER2-directed therapy and randomizing them to receive T-DM1 or T-DM1 with tuctanib. It will be interesting to know whether the addition of tucatinib will help improve overall events and decrease rates of CNS recurrence in patients with HER2-positive disease, concludes Tolaney.

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Neoadjuvant HER2+

Sara M. Tolaney, MD, MPH, discusses the unmet need with regard to effectively preventing central nervous system recurrence in HER2-positive breast cancer.