At the 2019 San Antonio Breast Cancer Symposium (SABCS), Rashmi Murthy, MD (University of Texas MD Anderson Cancer Center, Houston, United States), presented results from the randomized phase III HER2CLIMB trial, which evaluated the addition of the HER2-targeting tyrosine kinase inhibitor (TKI) tucatinib to trastuzumab and capecitabine in 612 patients with progressive metastatic HER2-positive breast cancer (Abstract GS1-01). These results were simultaneously published in The New England Journal of Medicine.
The addition of tucatinib to standard therapy was associated with a significant improvement in progression-free survival (PFS) compared to standard therapy and placebo. The 1-year estimated PFS was 33.1% with tucatinib plus standard therapy and 12.3% with standard therapy alone (HR 0.54, P<.001). Tucatinib treatment also resulted in a significant improvement in median overall survival (OS), from 17.4 months with trastuzumab and capecitabine alone to 21.9 months with the addition of tucatinib (HR 0.66, P = .005).
Tucatinib was highly active in patients with brain metastases, which represented nearly half of the total trial population. Among these patients, the 1-year PFS was 24.9% with tucatinib plus standard therapy, compared to 0% with standard therapy alone (HR 0.48, P<.001). The median PFS was 7.6 months with tucatinib plus trastuzumab and capecitabine, compared to 5.4 months for trastuzumab and capecitabine alone.
The most common adverse events (AEs) associated with tucatinib treatment included diarrhea, hand-foot disease, nausea, fatigue, and vomiting. Grade 3/4 diarrhea occurred in 12.9% of patients receiving tucatinib plus standard therapy, and in 8.6% of patients treated with standard therapy alone.
Dr Murthy concluded that addition of tucatinib to trastuzumab and capecitabine resulted in significant and clinically meaningful improvements in PFS and OS among patients with metastatic HER2-positive breast cancer who had progressed on first-line therapy, and that this combination should be considered as a new standard for this population. Of note, this treatment combination was highly active in patients with brain metastases, which represent a high-risk and difficult-to-treat patient population.
Read more about this study on Medscape Medical News.
N Engl J Med. 2019 Dec 11. [Epub ahead of print.]