NEW YORK – AstraZeneca on Monday said it will share interim data with regulatory authorities from the Phase III DESTINY-Breast09 trial, in which patients with HER2-positive metastatic breast cancer on Enhertu (trastuzumab deruxtecan) and Genentech's Perjeta (pertuzumab) as a frontline treatment fared better than those on two HER2-targeted monoclonal antibodies plus chemotherapy.
In DESTINY-Breast09, researchers are comparing Enhertu, codeveloped by AstraZeneca and Daiichi Sankyo, plus Perjeta against standard treatment with taxane, Genentech's Herceptin (trastuzumab), and Perjeta in more than 1,100 patients with hormone receptor (HR)-positive or -negative, HER2-positive breast cancer who have not previously received chemotherapy and have had up to one previous line of endocrine therapy in the metastatic setting. Patients who've received HER2-targeted therapy in the neoadjuvant or adjuvant setting are eligible for the trial if it has been more than six months between when they were diagnosed with metastatic disease and when they received anti-HER2 treatment. Researchers are also stratifying patients based on HR and PIK3CA mutation status.
In terms of progression-free survival, the primary outcome measure of the trial, patients on the Enhertu combo had a "significant and clinically meaningful improvement" compared to the standard-of-care arm, according to AstraZeneca. Overall survival data were not mature at the time of the interim analysis but showed an early trend favoring Enhertu-Perjeta.
In a second arm of the trial, researchers are comparing Enhertu monotherapy to Herceptin, Perjeta, and taxane. This arm remains blinded and will read out when the progression-free survival analysis is finalized, according to AstraZeneca.
"This is the first trial in more than a decade to demonstrate superior efficacy across a broad HER2-positive metastatic breast cancer population compared to the current first-line standard of care," Susan Galbraith, AstraZeneca executive VP of oncology hematology R&D, said in a statement. "This is a significant milestone for patients and sets the foundation for Enhertu in combination with pertuzumab as an important treatment option in the first-line HER2-positive setting."
In May 2022, the US Food and Drug Administration approved Enhertu as a second-line therapy for patients with advanced HER2-positive breast cancer who have received an anti-HER2-based regimen either in the metastatic setting or in the neoadjuvant setting based on data from the DESTINY-Breast-03 trial. Enhertu is also approved in the US, Europe, and other countries in a number of other indications, including HER2-positive gastric cancer, HER2-low and -ultralow breast cancer, and as tumor-agnostic therapy for metastatic HER2-positive solid tumors.