Enhertu Regimen Improves Responses in High-Risk HER2+ Breast Cancer

Enhertu (fam-trastuzumab deruxtecan-nxki) followed by Taxol (paclitaxel), Herceptin (trastuzumab) and Perjeta (pertuzumab), also known as THP, showed a statistically significant and clinically meaningful improvement in pathologic complete response rates compared with standard-of-care treatment (dose-dense doxorubicin and cyclophosphamide followed by THP) when used before surgery in patients with high-risk, locally advanced HER2-positive early-stage breast cancer.

These high-level findings come from the phase 3 DESTINY-Breast 11 trial, which is assessing neoadjuvant Enhertu monotherapy or Enhertu plus THP versus standard care in high-risk HER2-positive early-stage breast cancer, according to a news release from AstraZeneca.

Pathologic complete response means no invasive cancer is found in the breast or lymph nodes after treatment and surgery.

“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,” Susan Galbraith, executive vice president, Oncology Hematology R&D, AstraZeneca, said in the news release. “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.”

In addition, the secondary end point of event-free survival (EFS) was not mature at the time of analysis, but data showed an early positive trend favoring Enhertu followed by THP compared with standard care. The trial will continue to monitor EFS.

Regarding side effects, Enhertu followed by THP was associated with a more favorable safety profile than standard of care, with no new safety concerns reported and consistent findings across both treatment arms. Rates of interstitial lung disease were comparable between groups, based on independent review.

Study results will be presented at an upcoming medical meeting and shared with regulatory authorities.

“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, global head, R&D, Daiichi Sankyo, said in the news release, “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."

AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low, and HER2-ultralow metastatic breast cancer with Enhertu, exploring its potential in earlier treatment lines and new breast cancer settings, according to the news release.

Enhertu and High-Risk, HER2-Positive Early-Stage Breast Cancer

Enhertu is a HER2-directed DXd antibody-drug conjugate (ADC) developed by Daiichi Sankyo and co-commercialized by AstraZeneca and Daiichi Sankyo. It has shown improved outcomes in six phase 3 breast cancer trials across various subtypes and stages, including the DESTINY-Breast09 phase 3 trial in the first-line HER2-positive metastatic setting. Enhertu is also being studied in ongoing trials, including the DESTINY-Breast05 phase 3 trial, which evaluates its use in the high-risk adjuvant early HER2-positive setting.

Approximately one in three patients with early-stage breast cancer are at high risk due to a higher chance of recurrence and poor prognosis. Achieving pathological complete response in HER2-positive breast cancer is linked to better long-term outcomes. Current standard care often involves combination chemotherapy, including anthracyclines, which can be difficult to tolerate and may cause long-term cardiovascular issues. Nearly half of patients do not achieve pathological complete response with neoadjuvant treatment, highlighting the need for new options.

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