WILMINGTON, Del. — AstraZeneca and Daiichi Sankyo said the U.S. Food and Drug Administration has approved ENHERTU for two new indications in patients with HER2-positive early breast cancer.
The approvals cover use of ENHERTU before surgery and after surgery, moving the drug into the curative-intent treatment setting for certain patients with early-stage HER2-positive breast cancer.
In the neoadjuvant setting, ENHERTU followed by a taxane, trastuzumab and pertuzumab was approved for adults with HER2-positive Stage II or Stage III breast cancer. In the adjuvant setting, ENHERTU was approved for adults with HER2-positive breast cancer who have residual invasive disease after trastuzumab, with or without pertuzumab, and taxane-based treatment.
The approvals were based on results from the Phase III DESTINY-Breast11 and DESTINY-Breast05 trials.
“HER2-positive breast cancer is an aggressive disease, and our goal is to reduce the risk of recurrence for patients as early as possible to achieve the best long-term outcomes,” said Shanu Modi, M.D., Medical Oncologist, Memorial Sloan Kettering Cancer Center. “The neoadjuvant setting offers the earliest opportunity to improve outcomes, while the adjuvant setting provides another important chance to prevent recurrence for patients with residual disease after surgery. These two new indications in HER2-positive early breast cancer will evolve how we treat patients in these settings and support trastuzumab deruxtecan as a potential new standard of care in early-stage disease.”
In DESTINY-Breast11, ENHERTU followed by the THP regimen produced a pathologic complete response rate of 67.3%, compared with 56.3% for dose-dense doxorubicin and cyclophosphamide followed by THP. The result represented an 11.2% improvement.
In DESTINY-Breast05, ENHERTU reduced the risk of invasive disease recurrence or death by 53% compared with trastuzumab emtansine in patients with HER2-positive breast cancer who had residual invasive disease after neoadjuvant therapy. At three years, 92.4% of patients in the ENHERTU arm were alive and free of invasive disease, compared with 83.7% of patients in the trastuzumab emtansine arm.
Dave Fredrickson, executive vice president of AstraZeneca’s Oncology Haematology Business Unit, said the approvals address an ongoing need for more treatment options in early disease.
“HER2-positive early disease is considered highly curable, however up to one in four patients still experience disease recurrence, underscoring the need for new options in this setting. These approvals mark an important step forward, expanding the possibility of cure to more patients for the first time in many years and positioning ENHERTU as a foundational treatment in early breast cancer,” Fredrickson said.
Ken Keller, global head of oncology business and president and CEO of Daiichi Sankyo Inc., said ENHERTU is now approved in the U.S. across both early and metastatic HER2-positive breast cancer.
“ENHERTU has redefined the treatment of HER2-expressing breast cancer with practice-changing data across six breast cancer indications in seven years. ENHERTU is now approved in the US across both early and metastatic HER2-positive breast cancer, accomplishing what we set out to achieve a little over a decade ago for patients at the start of our comprehensive clinical development program,” Keller said.
Victoria Smart, senior vice president of mission at Susan G. Komen, said additional early breast cancer treatment options could help reduce progression to metastatic disease.
“Providing patients with early breast cancer more options to help prevent progression to metastatic disease can lead to improved outcomes. Progression and recurrence remain among the most significant unmet needs for those diagnosed with early breast cancer, and continued advances in treatment bring new hope to patients and families facing this disease,” Smart said.
The companies said no new safety concerns were identified in either trial. In DESTINY-Breast11, ENHERTU followed by THP had similar rates of drug-related adverse events and interstitial lung disease or pneumonitis as the comparator regimen, with lower rates of several serious or high-grade adverse events. In DESTINY-Breast05, ENHERTU and trastuzumab emtansine had similar rates of overall drug-related adverse events and Grade 3 or higher adverse events, though adjudicated drug-related interstitial lung disease or pneumonitis was higher in the ENHERTU arm.
ENHERTU is a HER2-directed antibody drug conjugate discovered by Daiichi Sankyo and jointly developed and commercialized by AstraZeneca and Daiichi Sankyo. The drug is already approved in more than 95 countries, including the U.S., for patients with HER2-positive metastatic breast cancer.
AstraZeneca will pay Daiichi Sankyo $155 million in milestone payments tied to the two U.S. approvals. Sales of ENHERTU in the U.S. are recognized by Daiichi Sankyo.
