A Close Look at Tucatinib in HER+ Breast Cancer

Rita Nanda, MD: Tucatinib was recently approved in conjunction with trastuzumab and capecitabine to be given in the second-line or third-line setting for patients who have HER2-positive metastatic breast cancer. The approval was based on the findings from the HER2CLIMB randomized phase 3 trial. As you’ll recall, this was a phase 3 trial that randomized patients to tucatinib, trastuzumab, and capecitabine, or a placebo, trastuzumab, and capecitabine. Patients were randomized in a 2:1 fashion to the triplet, versus capecitabine and trastuzumab with the placebo. What was found was a significant improvement in progression-free survival of more than 2 months, and very remarkably, improvement in overall survival by almost 6 months for those patients who got tucatinib in conjunction with capecitabine and trastuzumab. This has been practice changing. What was interesting was that the trial enrolled a significant proportion of patients with brain metastases. Almost half of the patients who participated in this trial had brain metastases, either previously treated or previously untreated, and even progressive. As long as patients didn’t require urgent management of their intercranial metastases, they were allowed to enroll in HER2CLIMB. In those patients who had brain metastases, there was a similar improvement seen in progression-free survival, which is remarkable given how poor a prognosis is with patients who have CNS [central nervous system] metastatic disease. This has given a lot of options for patients who have intercranial brain metastases.

In patients with brain metastases who participated in HER2CLIMB, their response rate when tucatinib was added to trastuzumab plus capecitabine was more than double was it was with trastuzumab and capecitabine alone. Forty-seven percent of patients who had intercranial disease had intercranial response to therapy, which was much higher than what we saw with the capecitabine and trastuzumab alone, where the response rate was only 20%. I think this is a very important option for those patients with brain metastases and could very well lead to a delay in needing radiation, and certainly associated with a much better quality of life. As someone who’s used tucatinib as part of the HER2CLIMB trial, I had a number of patients who participated in the trial with brain metastases. After they were unblinded, I found out that they did in fact receive tucatinib, and actually had very nice response intracranially to the regimen. So, I think it’s a really exciting regimen to be able to offer patients, particularly those with brain metastases, because it may help to delay the need for radiation.

Transcript Edited for Clarity