Less than three weeks after AstraZeneca and Daiichi Sankyo reported positive results for oncology powerhouse Enhertu in a first-line breast cancer trial, the companies have scored again in another phase 3 breast cancer study.
The Destiny-Breast11 trial has shown that Enhertu followed by the chemotherapy pacliotaxel, and targeted cancer drugs Herceptin and Perjeta (THP) provides a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) versus standard of care (SOC) when used before surgery in patients with high-risk, locally advanced HER2-positive early-stage breast cancer.
SOC in this indication includes chemotherapies doxorubicin and cyclophosphamide, followed by the THP regimen.
The companies explained that pCR is defined as no evidence of invasive cancer cells in the removed breast tissue and lymph nodes following treatment. This is the first phase 3 trial of Enhertu to show its benefit in early 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,” Susan Galbraith, who heads up oncology hematology R&D for AZ, said.
The companies said they will share the data with regulatory authorities and present them at a future medical conference.
While data for the secondary endpoint of event-free survival (EFS) was not mature, it did show an early trend favoring the Enhertu arm. Investigators will continue to follow EFS in the study, the companies said.
Roughly one in three patients with early-stage breast cancer are considered high risk, as they are more likely to experience disease recurrence and have a poor prognosis, the companies said. Achieving pCR in early-stage HER2-positive breast cancer is associated with improved long-term outcomes.
“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,” Ken Takeshita, Daiichi’s R&D chief, said in a release, adding that the results “could offer patients with HER2-positive breast cancer a promising new treatment approach prior to surgery.”
In the trial, the Enhertu group showed an improved safety profile versus SOC. The safety data remained consistent with previous profile data for Enhertu and the THP treatments.
The announcement comes after the companies reported successful results from the Destiny-Breast09 trial in which Enhertu and Roche’s Perjeta topped THP in delaying tumor progression or death in patients with newly diagnosed HER2-positive metastatic breast cancer. Backed by the data, AZ and Daiichi are preparing submissions for Enhertu as a first-line treatment in the indication.
Enhertu also is under investigation in several other ongoing breast cancer trials, including the Destiny-Breast05, which is evaluating the treatment in the high-risk adjuvant early HER2-positive setting.
The antibody drug conjugate (ADC) was first approved in 2019 for third-line use in patients with HER2-positive unresectable or metastatic breast cancer. The companies have tacked on six FDA label expansions since, including a January endorsement for patients with HER2-low or HER2-ultralow metastatic breast cancer.
Enhertu logged sales of $3.75 billion in Daiichi’s 2024 fiscal year, which concluded at the end of March. The company is projecting sales of the treatment to reach 662 billion Japanese yen in this fiscal year ($4.6 billion).