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Opinion: Novel Therapies Show Promise in Treatment of Metastatic HER2-Positive Breast Cancer

Breast medical oncologist Priyanka Sharma, MD, highlights emerging treatments for metastatic HER2-positive breast cancer in editorial published in The New England Journal of Medicine.

February 24, 2020

An NEJM editorial authored by Priyanka Sharma, MD, professor of medicine and breast medical oncologist at The University of Kansas Cancer Center and vice chair of SWOG Breast Committee, recaps recent major advances in the treatment of metastatic HER2-positive breast cancer. Published in The New England Journal of Medicine, Dr. Sharma highlighted two studies evaluating novel drugs as third-line or later therapy for metastatic HER2-positive breast cancer.  

HER2CLIMB Clinical Trial

In the HER2CLIMB phase 2 study, women who were treated with tucatinib, an investigational oral HER2 tyrosine kinase inhibitor, as well as Herceptin and capecitabine, lived longer than those who received only Herceptin and capecitabine

According to Dr. Sharma, these encouraging findings will lead to a change in standard of care.

“Patients in the tucatinib-combination group had a 34% lower risk of death compared to those in the control group. The addition of tucatinib also increased progression-free survival in those with brain metastases,” she said. “This is a very exciting finding because we desperately need effective treatment strategies for brain metastasis.”

DESTINY-Breast01 Clinical Trial

In the DESTINY-Breast01 clinical trial, investigators tested trastuzumab deruxtecan, a novel antibody-drug conjugate. Though not compared against another treatment, the results were very promising. Patients in this trial had received multiple prior lines of treatment and had a response rate of 60.9% with a median duration of progression-free survival of about 16 months. 

The therapy, however, did lead to increased risk of serious lung-related side effects, experienced by 13.6% of study participants and resulting in four deaths. In the editorial, Dr. Sharma noted that future studies should further explore etiology and management strategies for this toxic side effect to reduce its incidence and severity. Trastuzumab deruxtecan was approved by the U.S Food and Drug Administration in December 2019 for the treatment of patients with metastatic HER2 positive breast cancer.

“Availability of these new and more effective agents will change the way we treat patients with metastatic HER2-positive breast cancer who have already gone through several lines of treatment,” Sharma said. “As we incorporate such novel drugs into treatment, we must consider the patient’s health status, as well as cost and access.”


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