Pretreated Patients with HER2-Positive Metastatic Breast Cancer See Benefit from Investigational Drug

Sixty percent of patients with pretreated HER2-positive metastatic breast cancer had a partial or complete response to an investigational HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd), according to study results presented at the San Antonio Breast Cancer Conference and published simultaneously in the New England Journal of Medicine on December 11.

In the phase 2 study, T-DXd was given to 184 patients who had undergone a median of six previous treatments with Kadcyla (T-DM1) and other HER2-targeted treatments. A response to the therapy was reported in about 60.9% of patients — 6% with complete responses and 54.9% with partial responses. The median duration of patients’ response to the therapy was 14.8 months, and the median duration of progression-free survival, or the length of time during and after the treatment that patients lived with their disease, but their disease didn’t get worse, was 16.4 months.

The disease control rate was 97%, which suggests that the vast majority of cancers in this population seem to have at least some sensitivity to T-DXd, according to the study’s lead author, Dr. Ian Krop, associate chief of the Division of Breast Oncology at Dana-Farber Cancer Institute in Boston.

Data from this phase 2 study support the findings of a prior phase 1 study of T-DXd, which showed that T-DXd yielded an objective response rate of 59% in patients with advanced HER2- positive breast cancer previously treated with Kadcyla. The Food and Drug Administration (FDA) granted priority review to T-DXd in October 2019.

HER2 positive describes cancer cells that have too much of a protein called HER2 on their surface. In normal cells, HER2 helps to control cell growth. But when it is made in larger than normal amounts by cancer cells, the cells may grow more quickly and be more likely to spread to other parts of the body.

Although many patients in the phase 2 trial saw promising clinical responses to T-DXd, 99% of patients also experienced treatment-emergent side effects — unexpected medical problems that happen during treatment, which can be mild, moderate or severe. Fifty-seven percent of patients experienced side effects categorized as grade 3 or higher, such as decreased neutrophil count, nausea, anemia, decreased lymphocyte count and fatigue. Side effects forced 15% of patients to discontinue treatment.

Among the more severe side effects, interstitial lung disease (ILD), which causes scarring of the lungs and difficulty breathing, was observed in 25 patients, four of which died from the complication. “ILD is a serious concern in patients treated with T-DXd,” Krop said in a press briefing. “Why we are seeing this particular risk is unclear, but clearly we need to do more in terms of research to identify those patients who are at highest risk of ILD.”

Despite these risks, Krop added that the high rate of durable responses observed in patients taking T-DXd suggests that this antibody-drug conjugate could provide a new treatment option for patients with HER2-positive metastatic breast cancer.

“This study is looking at patients who are already four or five years out from their original diagnosis of breast cancer,” Krop said. “Here, other drugs haven’t been very effective. That’s why having new therapies that are active in this heavily pretreated population is very helpful for our patients.”