Two new drugs in clinical trials are extending survival for women with metastatic HER2-positive breast cancer that had progressed with previous treatment. One of the drugs was effective for brain metastasis, which is particularly difficult to treat. Results from both studies were reported in the New England Journal of Medicine.  

The HER2CLIMB trial randomized 612 patients to receive either the investigational drug (tucatinib) plus capecitabine and trastuzumab or a placebo and the capecitabine-trastuzumab combination. Progression-free survival was 7.8 months in the tucatinib group compared to 5.6 months in the placebo group. Additionally, tumors shrunk in 41% of women in the tucatinib group versus 23% of the placebo group, and at two years, 45% of women receiving tucatinib were still alive compared to 27% receiving placebo. Notably, 25% of those with brain metastasis in the tucatinib group were alive with no disease progression at one year, compared to 0% in the placebo group.  

In the DESTINY-Breast 01 trial, all 184 participants received trastuzumab deruxtecan, an antibody-drug conjugate that chemically combines a monoclonal antibody with a cancer-killing agent. All showed some reduction in tumor size, with 61% experiencing substantial reductions and several achieving a complete response. Based on the findings, the U.S. Food and Drug Administration granted trastuzumab deruxtecan accelerated approval in December 2019. Although most of the treatment-related side effects were mild, the approval indicated a special warning for clinicians about increased risk of interstitial lung disease, which resulted in 15% of the trial participants discontinuing treatment. Four patients died from the lung disease.