A Phase 1b clinical trial investigating tucatinib combined with ado-trastuzumab emtansine (T-DM1) in advanced ERBB2/HER2-positive metastatic breast cancer has yielded encouraging results.
Treatment options for patients with disease progression after treatment with trastuzumab, pertuzumab, and T-DM1 are currently limited.
In this study, a multi-institutional group of researchers wanted to determine the maximum tolerated dosage of tucatinib in combination with T-DM1, in the treatment of patients with ERBB2/HER2-positive metastatic breast cancer with and without brain metastases.
To achieve this, they conducted a Phase 1b open-label, multicenter, clinical trial. Fifty-seven participants with ERBB2/HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane enrolled.
The maximum tolerated dosage of tucatinib combined with ado-trastuzumab emtansine was found to be 300 mg administered orally twice daily. The findings were recently published in JAMA Oncology.
“It’s a no-chemo regimen. Once the drug is approved, we hope to see this regimen come forward in the course of treatment. Ultimately, we hope it will prevent recurrences and also diminish the number of brain metastatic recurrences,” first author Virginia Borges (University of Colorado Denver, CO, USA) explained.
The objective response rate was 48% and median progression-free survival was 8.2 months. Importantly, tucatinib acted against brain metastases stemming from HER2+ breast cancer, a major cause of mortality from the disease.
“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. It’s a pill. It works. And it hardly causes side effects. It’s really a doctor’s dream,” Borges commented.
Tucatinib is now being evaluated in a number of other trials and with additional partners, such as a trial exploring the use of the drug as a component of a combination against triple-positive breast cancer.
Borges hopes that the effectiveness of tucatinib in patients with metastatic disease who have tried previous treatments may lead to trials of the drug being used earlier in the course of treatment.
Updated results will be presented at the San Antonio Breast Cancer Symposium (4–6 December, TX, USA).