Sequencing Newer Agents in HER2-Positive Breast Cancer

Sara A. Hurvitz, MD, director of the Breast Cancer Clinical Research Program and co-director of the Santa Monica University of California Los Angeles (UCLA) Outpatient Hematology/Oncology Practice, as well as an assistant professor of medicine in the Division of Hematology/Oncology of the David Geffen School of Medicine at UCLA, discusses sequencing the current therapies for patients with HER2-positive breast cancer.

Hurvitz says sequencing is tricky because there are not a lot of data to inform that type of decision. Taxane-based therapy with the combination of trastuzumab (Herceptin) and pertuzumab (Perjeta) is used in the first-line setting based on the findings from the CLEOPATRA study (NCT00567190). This will be the frontline standard until a new agent goes head-to-head against this combination.

The second-line standard is trastuzumab emtansine [T-DM1; Kadcyla] based on the EMILIA (NCT00829166) and TH3RESA trials (NCT01419197). The combination of tucatinib (Tukysa), capecitabine, and trastuzumab is also available for use in the second-line setting, but it wasn’t compared directly with T-DM1 in the HER2CLIMB trial (NCT02614794). Hurvitz says she would reserve the use of that regimen for patients who have central nervous system metastases.

There are many regimens available in the third-line setting, and the sequencing of these options hasn’t been tested in a randomized clinical trial yet. Right now, sequencing is based on tolerability, the toxicity profile, and the data relating to the agents. Many physicians would use trastuzumab deruxtecan as our third-line agent of choice, but that may be moving up into earlier-line settings as new data accumulate from the phase 3 trials that are ongoing, according to Hurvitz.