Dr Nye on Future Treatment Directions in HER2+ Breast Cancer Brain Metastases

Lauren E. Nye, MD, breast medical oncologist, clinical medical director, Breast Cancer Prevention, the University of Kansas Cancer Center, discusses future directions for the treatment of patients with HER2-positive breast cancer with brain metastases.

Dr Nye chaired an OncLive State of the Science Summit™ (SOSS) on breast cancer, during which her colleague Ryan K. Rader, MD, gave a presentation on updates in HER2-positive metastatic breast cancer. In this presentation, Rader discussed the evolving use of the antibody-drug conjugates ado-trastuzumab emtansine (T-DM1; Kadcyla) and fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in patients with HER2-positive breast cancer, as well as future directions for these therapies, Nye says.

Additionally, emerging data have shown the potential for improved treatment modalities in patients with HER2-positive disease with brain metastases, Nye explains. In cohorts 1, 2, and 3 of the phase 2 DEBBRAH trial (NCT04420598), which evaluated T-DXd in patients with HER2-positive advanced breast cancer with active brain metastases, the overall intracranial overall response rate (IC-ORR) was 46.2% (95% CI, 19.2%-74.9%). Furthermore, the single-arm, phase 2 TUXEDO-1 trial (NCT04752059), which assessed T-DXd in patients with HER2-positive breast cancer with brain metastases, showed an IC-ORR of 73.3% (95% CI, 48.1%-89.1%) in the intent-to-treat population (n = 15). This included a 13.3% complete response rate and a 60% partial response rate. In the future, more clinical trials should include patients with brain metastases to further the breast cancer field’s understanding of which agents are most effective for this disease state, Nye emphasizes.

During the SOSS, Rader also discussed the D-TORCH trial (CTRI/2021/01/030592), which investigated the use of topical 1% diclofenac (Voltaren) gel to prevent capecitabine (Xelox)-induced hand-foot syndrome in patients with breast and gynecologic cancers, Nye notes. In the breast cancer subgroup, 7.8% of patients in the diclofenac arm (n = 77) developed any-grade hand-foot syndrome vs 19.7% of those in the placebo arm (n = 71; P = .034). Breast oncologists are interested in implementing the D-TORCH findings in their clinical practice to prevent hand-foot syndrome in patients receiving capecitabine, Nye concludes.