Invited discussant Ciara O’Sullivan, MB, BCh, BAO, of Mayo Clinic, Rochester, Minnesota, commented on the DESTINY-Breast03 trial at the 2021 San Antonio Breast Cancer Symposium. “The treatment of HER2-positive disease is an evolving landscape, with eight approved agents. Despite this rapid progress, there are still outstanding issues, such as defining markers of therapeutic resistance,” she said.

Ciara O’Sullivan, MB, BCh, BAO

“The first-line standard of care remains a taxane plus trastuzumab plus pertuzumab. However, second-line options have rapidly evolved. [Ado-trastuzumab emtansine (T-DM1)] has been approved based on the EMILIA trial. More recently, the [National Comprehensive Cancer Network] has listed tucatinib, capecitabine, and trastuzumab as a second-line treatment option. The striking results of the DESTINY-Breast03 trial are also changing the treatment paradigm,” Dr. O’Sullivan continued.

“T-DM1 is currently approved for patients who have received one or more prior therapies. The consistent progression-free survival and objective response rate benefits we saw in DESTINY-Breast03, plus the substantial improvement in the central nervous system response rate, support the use of [fam-trastuzumab deruxtecan-nxki (T-DXd)] as a new second-line standard of care for patients with HER2-positive metastatic breast cancer. The question moving forward is, what is the best treatment for patients with HER2-positive breast cancer who have brain metastasis,” Dr. O’Sullivan told listeners. “It remains to be seen whether tucatinib or T-DXd can prevent brain metastasis, and adjuvant trials will answer this question.”

Ongoing trials are incorporating T-DXd and tucatinib as front-line therapy, and the combination is also being evaluated in HER2-positive metastatic breast cancer. 

DISCLOSURE: Dr. O’Sullivan has received research funding from Lilly, Seagen, Bavarian Nordic, Minnemarita Therapeutics, and Biovica.