Dr. Hamilton on the HER2CLIMB Trial in Metastatic HER2+ Breast Cancer

Erika P. Hamilton, MD, director, Breast Cancer and Gynecologic Research Program, Sarah Cannon Research Institute, discusses the phase II HER2CLIMB trial in metastatic HER2-positive breast cancer.

In the phase II trial, heavily pretreated patients with locally advanced unresectable or metastatic HER2-positive disease were randomized to receive tucatinib combined with trastuzumab (Herceptin) and capecitabine (Xeloda) versus trastuzumab and capecitabine alone. Tucatinib is an oral TKI that selectively inhibits HER2, and as such, it has less off-target toxicity compared with other TKIs like neratinib (Nerlynx) and lapatinib (Tykerb), explains Hamilton.

There were several primary end points, including progression-free survival (PFS), overall response rate, overall survival, and PFS in patients with brain metastases. Each end point favored the addition of tucatinib, says Hamilton. Twenty-five percent of patients with brain metastases who received tucatinib were on therapy at 1 year versus 0% of those who received trastuzumab and capecitabine alone.

Notably, the trial allowed patients with previously treated, but stable, brain metastases to enroll, as well as those with asymptomatic and untreated brain metastases and those with symptomatic and progressive brain metastases, concludes Hamilton.