Novel Combination Therapy for ERBB2/HER2-Positive Metastatic Breast Cancer
Posted: Wednesday, September 19, 2018
For patients with ERBB2/HER2-positive metastatic breast cancer, the combination of the HER2-specific tyrosine kinase inhibitor tucatinib with the antibody-drug conjugate ado-trastuzumab emtansine (formerly known as T-DM1) holds therapeutic potential. The findings of a phase Ib clinical trial of this novel combination therapy were published in JAMA Oncology, with an emphasis on the combination’s tolerable toxicity and preliminary activity.
“One of the best things about this drug is that it combines well with nearly everything. It is so well tolerated that when you test tucatinib in combination with other drugs, it feels like you’re just giving the other drug,” revealed Virginia F. Borges, MD, MMSc, of the University of Colorado Cancer Center, in a news release from Colorado Cancer Blogs.
The clinical trial included 57 patients with metastatic ERBB2/HER2-positive breast cancer who received prior HER2 therapy with trastuzumab and a taxane. With the combination of tucatinib and ado-trastuzumab emtansine, 48% of patients achieved an objective response, and there was a median progression-free survival of 8.2 months. Additionally, the researchers noted that tucatinib seemd to counter brain metastases, a leading cause of death from HER2-positive breast cancer.
As for toxicity, among the 50 patients treated with the maximum tolerated dosage (300 mg twice daily), nearly three-quarters experienced nausea. Diarrhea and fatigue were reported by more than half of the treated patients. Dr. Borges and colleagues noted that the majority of adverse events were grade 1 or 2.
Further clinical trials investigating tucatinib alone, in combination with ado-trastuzumab emtansine, or other variations are warranted, according to the investigators. Updated study results are expected to be presented at the upcoming 2018 San Antonio Breast Cancer Symposium.
