Phase III Triumph for AstraZeneca and Daiichi Sankyo's Enhertu in Early-Line Breast Cancer

AstraZeneca and Daiichi Sankyo have announced preliminary results from the Phase III DESTINY-Breast06 trial, highlighting the effectiveness of their antibody-drug conjugate, Enhertu (trastuzumab-deruxtecan), in metastatic breast cancer patients. The study, which involved over 860 participants, compared Enhertu to a selection of chemotherapies, such as capecitabine, paclitaxel, or nab-paclitaxel, in individuals with hormone receptor (HR) positive status and low to ultralow HER2 protein expression who had received prior endocrine therapy.

The findings indicated that patients treated with Enhertu experienced a significant improvement in progression-free survival (PFS), a benefit that was consistent among those with low HER2 expression levels. Although the overall survival (OS) data was not yet mature at the time of the interim analysis, there was an early indication of an OS improvement with Enhertu compared to standard chemotherapy, particularly noticeable in the subgroup with low HER2 expression.

The DESTINY-Breast06 trial will proceed as planned to further evaluate OS and other secondary outcomes. AstraZeneca's executive vice president of oncology R&D, Susan Galbraith, stated that the results support the potential of Enhertu to become a new standard of care for metastatic breast cancer with low or ultralow HER2 expression after endocrine treatment. She also emphasized Enhertu's potential across the spectrum of HR-positive breast cancer, suggesting a redefinition of metastatic breast cancer treatment.

While specific data from the study were not disclosed in the announcement, AstraZeneca and Daiichi Sankyo plan to present the findings at an upcoming medical conference and share them with global regulatory authorities for potential label expansion. Enhertu, developed using Daiichi Sankyo’s DXd ADC platform, targets the HER2 protein, which is linked to the rapid growth and division of cancer cells. The drug carries a payload of topoisomerase I inhibitors to induce cell death and was initially approved by the FDA in December 2019 for treating HER2-positive breast cancer. Recently, it also gained the FDA’s first tumor-agnostic ADC approval, expanding its use to HER2-positive solid tumors with no other treatment options available.