Enhertu (trastuzumab deruxtecan) and Trodelvy (sacituzumab govitecan), two antibody-drug conjugates (ADCs) currently approved for treatment-experienced patients, also delay disease progression for women receiving initial treatment for advanced breast cancer. ADCs use monoclonal antibodies to deliver strong chemotherapy directly to tumors, helping to minimize side effects.

 

The DESTINY-Breast09 trial, which included 770 people with HER2-positive locally advanced or metastatic breast cancer, showed that first-line treatment with Enhertu plus Perjeta (pertuzumab) reduced the risk of disease progression or death by 44% over standard therapy. At two years, 70% of patients on Enhertu plus Perjeta were still alive without further disease progression, compared with 52% in the standard-therapy group.

 

The ASCENT-04/KEYNOTE-D19 trial enrolled 443 patients with previously untreated inoperable locally advanced or metastatic triple-negative breast cancer who were eligible for immunotherapy. Trodelvy plus the immune checkpoint inhibitor Keytruda (pembrolizumab) lowered the risk of progression or death by 35% compared with Keytruda plus chemotherapy. At the one-year mark, 48% of Trodelvy plus Keytruda recipients and 33% in the Keytruda plus chemotherapy group were still alive without disease progression.

 

In both Phase III trials, treatment was generally safe, but severe adverse effects were common. Some experts have suggested it may be feasible to use ADCs as part of an induction regimen followed by less intensive maintenance therapy.

 

Sara Tolaney, MD, MPH, of Dana-Farber Cancer Institute, who led both studies, said Enhertu and Trodelvy could become new frontline standards of care. “It is important that we work toward shifting these very effective novel drugs to the first line of therapy to move the needle and improve outcomes for these patients,” she says.