Findings from the phase III HER2CLIMB-02 trial presented at the San Antonio Breast Cancer Symposium showed that the addition of tucatinib (Tukysa) to trastuzumab emtansine (T-DM1, Kadcyla) extended progression-free survival (PFS) versus T-DM1 alone for previously treated patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including a positive trend in those with brain metastases.
In this exclusive MedPage Today video, investigator Sara A. Hurvitz, MD, of the Fred Hutchinson Cancer Center in Seattle, discusses results of the dual HER2-targeted approach.
Following is a transcript of her remarks:
HER2CLIMB-02 was a phase III randomized, placebo-controlled clinical trial evaluating whether tucatinib adds benefit when added to T-DM1. There are about 460 patients randomly assigned to T-DM1 plus tucatinib or T-DM1 plus placebo. Patients were eligible if they had previously received trastuzumab [Herceptin] and a taxane in any setting.
Interestingly, patients with brain mets [metastases] were allowed on this study, and 44% of patients enrolled had brain mets, half of whom had active brain mets.
The study indicated at the primary analysis that progression-free survival was significantly improved with the addition of tucatinib to T-DM1 by about 2 months with a hazard ratio of 0.76. There was a hierarchical testing design, so because the primary endpoint was positive we then tested overall survival at this first interim analysis. And that was not yet positive. The data are immature, there are only 53% of events recorded at this time, so we’ll be following overall survival long-term.
Progression-free survival in the population of patients with brain mets also showed a very clear trend for improvement with tucatinib, not formally tested because of that hierarchical design. So overall tucatinib really did appear to improve outcomes for patients, waiting on the overall survival evidence.
From a side effect profile, adding tucatinib to T-DM1 does increase the rate of grade 3 or greater events and treatment discontinuations. Notably, there are more grade 3 or greater transaminase elevations. There are higher rates of diarrhea and vomiting. So monitoring patients closely if this regimen is approved in the future will be important. These were reversible events with discontinuation or treatment holds.