Sara Hurvitz, MD, FACP, shares insights into the results of the HER2CLIMB-02 trial, which saw patients with HER2-positive breast cancer benefit from the addition of tucatinib to trastuzumab emtansine (T-DM1).
Sara Hurvitz, MD, FACP, professor at the University of Washington and senior vice president of the Clinical Research Division at Fred Hutch, details the results and implications of the HER2CLIMB-02 trial, which evaluated the use of tucatinib and trastuzumab emtansine (T-DM1) in previously treated patients with HER2-positive metastatic breast cancer.
This transcript has been lightly edited.
AJMC: What was the key objective and design of the HER2CLIMB-02 trial?
Hurvitz: The HER2CLIMB-02 clinical trial is a phase 3 randomized study which aimed to evaluate whether adding tucatinib to T-DM1 improves outcomes for patients with HER2-positive advanced breast cancer. Approximately 460 patients were enrolled and randomized to receive either T-DM1 with tucatinib or T-DM1 with placebo. Eligible patients included those patients who had HER2-positive, locally advanced, unresectable or metastatic breast cancer, who had received prior trastuzumab and taxane in any setting. It's notable that patients with brain metastases, including stable or untreated or progressive brain metastases, were allowed on this clinical trial, similar to HER2CLIMB. The primary end point was progression-free survival [PFS] by investigator assessment. There were secondary end points and, due to alpha controlling and a hierarchical design, it was set that if the primary end point of PFS was met at the primary analysis, then the first of 2 overall survival analyses would be evaluated at the time of that reporting.
AJMC: How does the safety and efficacy profile of this treatment compare to other existing therapies for this patient population?
Hurvitz: In this clinical trial, patients were enrolled who had not received prior T-Dxd— trastuzumab deruxtecan—and this study did not compare the efficacy or safety of T-DM1 with tucatinib to trastuzumab deruxtecan, so we don't have a direct trial comparison to tell us the relative benefits and safety profile of these agents. Nor do we have a comparison of T-DM1 and tucatinib to the approved regimen of tucatinib with capecitabine and trastuzumab. So, at this point, we're having to use our best judgment in this clinical trial. We saw about a 2-month improvement in median [PFS] by adding tucatinib to T-DM1, and it was statistically significant. At the time of this reporting, there was not a statistically significant change in overall survival or improvement; there was no difference at this time. In terms of the adverse event profile, we're seeing more transaminase elevations by adding tucatinib to T-DM1, and slightly higher rates of diarrhea and cytopenias. These events were manageable by holding the dose or reducing the dose. So, this regimen does have a slightly different side effect profile when you look at the data relating to the HER2CLIMB regimen or to T-Dxd.
AJMC: Did any patient subgroups derive more benefit from the combination of tucatinib and trastuzumab emtansine?
Phillips: The prespecified subgroup analysis from this trial indicated, in general, the benefit with tucatinib was seen across these subgroups and looked similar to the overall patient population. So there wasn't a subgroup that we found, for example, who didn't appear to benefit from the use of tucatinib in this setting. I think it's going to be really important for us to dive down and look at biomarkers and look at the subgroup of patients who did have brain metastases, since that was a substantial proportion of the patient population, and look at things like the CNS [central nervous system] progression-free survival and intracranial objective response rates. There's a lot more work that's going to be done on this clinical trial.