AstraZeneca and Daiichi Sankyo announced that their Enhertu showed promise in treating people with high-risk, locally advanced HER2-positive early-stage breast cancer.
The announcement is based on results from DESTINY-Breast11, a global, multicentre, randomised, open-label Phase 3 clinical trial.
The study evaluated the efficacy and safety of Enhertu followed by THP against the standard regimen in patients with high-risk advanced HER2-positive early-stage breast cancer.
Participants received either eight cycles of Enhertu monotherapy, four cycles of Enhertu followed by four cycles of THP, or four cycles of dose-dense doxorubicin and cyclophosphamide (ddAC) followed by four cycles of THP.
The trial showed a significant improvement in pathologic complete response (pCR) rates when Enhertu was followed by paclitaxel, trastuzumab, and pertuzumab (THP), compared to the standard of care in the neoadjuvant setting.
Pathologic complete response, the primary endpoint of the trial, is defined as the absence of invasive cancer cells in breast tissue and lymph nodes post-treatment.
Secondary endpoints included event-free survival (EFS), invasive disease-free survival, overall survival, and safety.
While EFS data were not mature at the time of analysis, initial findings showed a positive trend favouring Enhertu followed by THP over the standard of care.
The trial will continue to monitor EFS outcomes. Enhertu followed by THP also demonstrated an improved safety profile compared to ddAC-THP.
Enhertu and THP showed safety profiles that were consistent with known profiles of the medication, with no new safety concerns identified.
Rates of interstitial lung disease were similar across the Enhertu followed by THP and ddAC-THP arms, as assessed by an independent adjudication committee.
Following recommendations from the Independent Data Monitoring Committee, patient enrolment in the third trial arm evaluating Enhertu alone was closed after an interim efficacy assessment.
Daiichi Sankyo R&D global head Ken Takeshita said: “There are still many patients with early-stage breast cancer who do not achieve a pathologic complete response with treatment in the neoadjuvant setting, increasing the risk of disease recurrence.
“These topline results from DESTINY-Breast11 demonstrate that Enhertu followed by THP could offer patients with HER2-positive breast cancer a promising new treatment approach prior to surgery, setting more patients on a path towards a potential cure.”
Enhertu is a HER2-directed DXd antibody drug conjugate (ADC), discovered by Daiichi Sankyo and is being jointly developed and marketed by AstraZeneca and Daiichi Sankyo.
The drug has been approved in over 75 countries for different breast cancer indications.
It is the lead ADC in Daiichi Sankyo’s oncology portfolio and the most advanced programme in AstraZeneca’s ADC platform.
AstraZeneca oncology haematology R&D executive vice president Susan Galbraith said: “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.
“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.”
