NEW YORK – AstraZeneca on Wednesday said it will share with regulators data from the DESTINY-Breast11 trial showing that the antibody-drug conjugate Enhertu (trastuzumab deruxtecan), followed by a chemotherapy and dual HER2-targeted regimen in the neoadjuvant setting, improved response rates compared to standard treatment in patients with high-risk, locally advanced, HER2-positive early-stage breast cancer.
In the Phase III trial, researchers are studying the efficacy and safety of neoadjuvant Enhertu, codeveloped by AstraZeneca and Daiichi Sankyo, as a single agent, or Enhertu followed by a combination of Genentech's anti-HER2 therapies Herceptin (trastuzumab) and Perjeta (pertuzumab) with the chemotherapy drug paclitaxel (the combination of the three drugs referred to as THP). The activity of these two arms are being compared to standard treatment, which comprised doxorubicin and cyclophosphamide followed by THP. Nearly a thousand patients were randomized to receive Enhertu monotherapy, Enhertu followed by THP, or chemo followed by THP.
In order to participate in the study, patients had to have HER2-overexpressing early-stage breast cancer at high risk of relapse, defined as lymph node-positive disease with a primary tumor stage T3 or T4.
AstraZeneca said patients on Enhertu followed by THP saw statistically significant and clinically meaningful improvement in their pathologic complete response rate compared to the group receiving standard treatment. In the Enhertu-THP arm, there was also an early trend toward improved event-free survival compared to the standard of care, although the data were not mature at the time of analysis.
According to AstraZeneca, nearly half of patients with early-stage, HER2-positive breast cancer do not achieve a pathologic complete response, and many experience long-term cardiovascular side effects due to anthracyclines in the standard regimen.
"The clinically meaningful improvement in pathologic complete response and the safety data seen in DESTINY-Breast11 highlight the potential of Enhertu to challenge the current standard of care in early-stage, HER2-positive breast cancer," Susan Galbraith, executive VP of oncology hematology R&D at AstraZeneca, said in a statement. "Enhertu is already an important treatment option in the metastatic setting, and these data have the potential to allow this medicine to move into early stages of disease where cure is possible."
The US Food and Drug Administration approved Enhertu in May 2022 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 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 in HER2-positive gastric cancer, in HER2-low and -ultralow breast cancer, and as a tumor-agnostic therapy for metastatic solid tumors.
AstraZeneca has also stated its intention to share interim data from the DESTINY-Breast09 trial with regulatory authorities demonstrating improved progression-free survival in patients with HER2-positive metastatic breast cancer who received Enhertu and Perjeta as frontline treatment compared to those on taxane, Herceptin, and Perjeta.