SABCS 2023: Combination of Two HER2-Targeted Agents in Advanced HER2-Positive Breast Cancer

By: Susan Reckling, MA
Posted: Thursday, December 7, 2023

Compared with the use of ado-trastuzumab emtansine (T-DM1) alone, the combination of the small-molecule inhibitor of HER2 tucatinib plus the antibody-drug conjugate T-DM1 extended progression-free survival in patients with unresectable, locally advanced or metastatic, HER2-positive breast cancer. These results from the HER2CLIMB-02 trial were presented by Sara A. Hurvitz, MD, of the University of Washington, Fred Hutchinson Cancer Center, Seattle, at the 2023 San Antonio Breast Cancer Symposium (Abstract GS01-10).

“This study is one of very few large breast cancer studies prospectively designed to evaluate novel systemic therapies in patients with brain metastases,” Dr. Hurvitz commented in an American Association for Cancer Research (AACR) press release. “Most studies evaluating systemic agents have been limited by a small size, a retrospective design, or an exploratory analysis of a larger study.”

In this phase III trial, 463 patients with unresectable, locally advanced or metastatic, HER2-positive breast cancer were randomly assigned to receive tucatinib plus T-DM1 (n = 228) or placebo plus T-DM1 (n = 235). At baseline, 44.1% had brain metastases.

The median time to disease progression or death was 9.5 months with tucatinib and 7.4 months without; the combination of tucatinib plus T-DM1 reduced the risk of disease progression or death by 24.1%. Among patients who had brain metastases at baseline, the median time to disease progression or death was 7.8 months with tucatinib and 5.7 months without; the combination of tucatinib plus T-DM1 reduced the risk of disease progression or death by 36.1%. After a median follow-up of 24.4 months, the overall survival data remain immature.

According to the investigators, the rate of certain treatment-related side effects, especially those linked to liver and gastrointestinal function, was higher among patients treated with tucatinib than in those treated with placebo, which resulted in a higher rate of dose adjustments and treatment discontinuation in the tucatinib arm. However, Dr. Hurvitz noted, these effects were largely manageable with monitoring and clinical intervention.

Disclosure: For full disclosures of the study authors, visit aacr.org.

San Antonio Breast Cancer Symposium

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