Enhertu Expands Reach in Breast Cancer Treatment with New FDA Approval

AstraZeneca and Daiichi Sankyo's antibody-drug conjugate (ADC) Enhertu has received expanded approval from the U.S. Food and Drug Administration (FDA) for the treatment of HER2-ultralow expressing breast cancer. This latest development positions Enhertu to potentially replace chemotherapy in a broader range of patients, marking a significant shift in breast cancer treatment paradigms.

Expanded Indication for HER2-Ultralow Breast Cancer

The FDA's decision on January 28, 2025, allows Enhertu to be used earlier and more broadly in patients with aggressive forms of breast cancer. Previously approved for HER2-low expressing tumors, Enhertu can now be administered to patients with "ultralow" HER2 expression levels, as determined by an FDA-approved test.

This expansion is particularly noteworthy as AstraZeneca estimates that up to two-thirds of hormone receptor-positive breast cancers typically classified as HER2-negative may actually have low levels of HER2 expression, with an additional 20% to 25% potentially falling into the "ultralow" category.

Clinical Data Supporting the Approval

The approval was based on compelling clinical trial results published in The New England Journal of Medicine. The study demonstrated that Enhertu delayed cancer progression or death by a median of 13.2 months, compared to 8.1 months for patients receiving chemotherapy. This translates to a 36% reduction in the risk of cancer progression for patients treated with Enhertu.

Importantly, similar results were observed in the subgroup of patients with ultralow HER2 levels, although the study was not specifically powered to detect a statistical difference in this population.

Implications for Breast Cancer Treatment

Ken Keller, President and CEO of Daiichi Sankyo, described the approval as "another paradigm shift in how certain breast cancers can be treated." The expanded indication for Enhertu challenges the traditional binary classification of HER2 status as either positive or negative, emphasizing the importance of viewing HER2 expression along a continuum.

Krissa Smith, Vice President of Education at Susan G. Komen, stressed the critical nature of this development, stating, "It is critical for patients to understand the HER2 status of their metastatic breast cancer to help them make informed treatment decisions."

This approval aligns with AstraZeneca and Daiichi Sankyo's broader strategy to position ADCs like Enhertu ahead of traditional chemotherapy in various tumor types. Mohit Manrao, Senior Vice President of AstraZeneca's U.S. oncology division, emphasized this goal, saying, "The key goal from this trial is to show the power of ADCs in truly replacing chemotherapy."