Dr. Pegram on Developing Agents for Patients With HER2+ Breast Cancer and Brain Metastases

Mark D. Pegram, MD, Susy Yuan-Huey Hung Professor, co-director, Stanford’s Molecular Therapeutics Program, director, Breast Cancer Oncology Program, Stanford Women’s Cancer Center, discusses developing agents for patients with HER2-positive breast cancer who have brain metastases.

Nancy U. Lin, MD, showed a paper at the 2017 ASCO Annual Meeting looking at high doses of trastuzumab (Herceptin) after passing the first step of a Simon’s Two-Stage design. The 40-patient, randomized phase II PATRICIA trial has completed enrollment and results are pending. There are also new small-molecule HER2-targeted agents that are more specific to HER2. They don’t show as much toxicity as other drugs, such as lapatinib (Tykerb) or neratinib (Nerlynx).

Tucatinib (ONT-380) is a pure HER2-directed therapy that doesn’t inhibit EGFR. It doesn’t result in diarrhea and skin rash to the extent of existing FDA-approved HER2-targeted agents. That molecule is in an ongoing randomized registration trial. Additionally, recently published data on FDA-approved trastuzumab emtansine (TDM-1; Kadcyla) show anecdotal responses and high tolerability.