The Benefits of Tucatinib in HER2+ Breast Cancer

Rita Nanda, MD: HER2CLIMB is a randomized phase 3 trial that has led to the FDA approval of tucatinib to be given in combination with trastuzumab and capecitabine. This trial demonstrated a significant improvement in progression-free survival as well as overall survival when tucatinib was added to capecitabine and trastuzumab in the second-line and third-line setting for patients with metastatic HER2-positive breast cancer. Almost half of the patients who participated in this trial had brain metastases at the time of study entry. Very remarkably, those patients with CNS [central nervous system] disease faired just as well as those patients who didn’t have brain metastases in terms of progression-free survival and overall survival. This is really remarkable as those patients who have CNS disease generally have a poor prognosis.

Tucatinib is a very important addition to our armamentarium for treating those patients with HER2-positive metastatic disease, particularly those with brain metastases. It’s got a very favorable safety and toxicity profile and is better than some of the other oral tyrosine kinase inhibitors that are used in conjunction with capecitabine for the treatment of patients with HER2-positive metastatic breast cancer to the CNS. Because tucatinib doesn’t target EGFR to the same degree as some of the other tyrosine kinase inhibitors, it isn’t as associated with diarrhea and rash as some other agents and is very well tolerated. In the pivotal phase 3 trial, the HER2CLIMB trial that led to the approval, there were very few patients who had to discontinue treatment because of toxicities. The vast majority of the toxicities were diarrhea and LFT [liver function test] elevations and were generally of low grade and easily managed. So, I think tucatinib, capecitabine, and trastuzumab is a very important regimen.

It's used for patients with brain metastases. It is very well tolerated, associated with a good quality of life, and improvement, not only in progression-free survival, but overall survival as well.

We are continuing to add to our armamentarium of drugs and regimens that we have available for patients with HER2-positive metastatic disease. Ultimately, patients do progress, and so there’s certainly a need to continue to develop new therapies to help those patients who have HER2-positive metastatic disease live longer and better. Tucatinib is a very important addition, particularly for those with CNS metastatic disease. But eventually these patients will progress, and newer strategies will be needed in the future.

Transcript Edited for Clarity