Enhertu scores again in early breast cancer

AstraZeneca and Daiichi Sankyo have chalked up another positive trial for their HER2-directed antibody-drug conjugate Enhertu in early breast cancer, this time in the 'post-neoadjuvant' setting.

The results of the DESTINY-Breast05 study showed a "highly statistically significant and clinically meaningful improvement" in invasive disease-free survival (IDFS) with Enhertu (trastuzumab deruxtecan) compared to Roche's Kadcyla (trastuzumab emtansine or T-DM1) in patients with HER2-positive breast cancer with residual disease in the lymph nodes and an increased risk of disease recurrence.

The result follows the DESTINY-Breast11 study, first revealed in May, which compared Enhertu followed by paclitaxel, trastuzumab, and pertuzumab (THP) to standard care of chemotherapy followed by THP as a neoadjuvant regimen for patients with high-risk, locally advanced HER2-positive early-stage breast cancer.

The latest result means that Enhertu has now outperformed standard therapies in two early breast cancer settings, and AZ and Daiichi Sankyo said they will now look at filing to expand the ADC's label to include neoadjuvant/post-neoadjuvant treatment.

Already a blockbuster therapy for advanced breast cancer and other indications like gastric cancer, Enhertu made revenues of $2.29 billion in the first half of this year, up 29% on the same period of 2024, and expanding into early breast cancer could lend additional momentum to the product.

Approximately half of patients with HER2-positive early breast cancer have residual disease after neoadjuvant treatment, putting them at an increased risk of disease recurrence, and some patients go on to develop advanced disease despite additional treatment in the post-neoadjuvant setting.

Once patients are diagnosed with metastatic disease, the five-year survival rate drops from nearly 90% to around 30%, according to AZ.

AZ's head of oncology and haematology R&D, Dr Susan Galbraith, said that DESTINY-Breast05 is the first trial to compare Enhertu directly with T-DM1 in early breast cancer.

"The results clearly show that Enhertu delivers superior outcomes, indicating that it may be a better option for patients," she added. "These results from DESTINY-Breast05, coupled with DESTINY-Breast11, underscore our commitment to moving Enhertu into early-stage HER2-positive breast cancer where patients can achieve sustained long-term outcomes, increasing the opportunity for cure."

Data from both DESTINY-Breast11 and DESTINY-Breast05 is due to be presented at the upcoming ESMO cancer congress in Berlin, Germany, on 18th October.

AZ and Daiichi Sankyo recently claimed their first approvals for a second ADC, TROP2-directed Datroway (datopotamab deruxtecan) as a treatment for patients with metastatic HR-positive, HER2-negative breast cancer who have previously been treated with endocrine therapy and at least one line of chemotherapy.

AstraZeneca has a target of $5 billion or more in peak annual sales for both Enhertu and Datroway as it chases a 2030 revenue target of more than $80 billion.