Tucatinib/T-DM1 Yield ‘Exciting’ Results in HER2+ Metastatic Breast Cancer

Key efficacy data from the phase 3 HERCLIMB-02 trial (NCT03975647) appear to support the use of tucatinib (Tukysa) plus trastuzumab emtansine (T-DM1; Kadcyla) as a treatment for those with metastatic HER2-positive breast cancer, Sara Hurvitz, MD, FACP, said in an interview with CancerNetwork^® at the 2023 San Antonio Breast Cancer Symposium (SABCS).

According to Hurvitz, senior vice president, director, and professor of the Clinical Research Division at Fred Hutch Cancer Center, the experimental regimen appeared to elicit a progression-free survival (PFS) benefit compared with placebo plus T-DM1, even among patients with brain metastases. She also noted that the overall survival data were immature at the time of the analysis and will later be confirmed as more survival events are observed.

Transcript:

What we presented was that the median progression-free survival was significantly improved in patients by about 2 months with a hazard ratio of 0.76; it was statistically significant [P = .0163]. Looking at the progression-free survival in the population of patients with brain metastases, again, we see a very nice just over 2-month improvement in median progression-free survival with the hazard ratio of 0.64.

This was not statistically tested due to the hierarchical testing design, but the first interim overall survival analysis was prompted by that positive PFS positive result. At this time, there was no significant difference between the 2 treatment arms. It’s important to know this analysis was quite immature with only 53% of the events needed, so we’ll be looking at overall survival when we hit 80% of survival events. It’s also important to note that post progression, half of the patients in each arm went on to receive trastuzumab deruxtecan [T-DXd; Enhertu]. This was a study that only enrolled patients who were naïve to T-DXd.

We know that T-DXd has substantial improvements in PFS and survival, so having so many patients receive this [agent] after progression is certainly going to impact our ability to observe survival differences. [Approximately] 15% of patients in each arm also went on to receive tucatinib. These are pretty exciting results for our patients, especially those with brain metastases. This study did enroll, as I said, patients with brain metastases, who comprised 44% or so of the entire population enrolled in this study. These are interesting data, and we’ll see if this regimen is ultimately approved.

Reference

Hurvitz S, Loi S, O’Shaughnessy J, et al. HER2CLIMB-02: randomized, double-blind phase 3 trial of tucatinib and trastuzumab emtansine for previously treated HER2-positive metastatic breast cancer. Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX; abstract GS01-10.