ENHERTU gains FDA approval for HER2 low or ultralow metastatic breast cancer treatment

Daiichi Sankyo and AstraZeneca‘s ENHERTU (fam-trastuzumab deruxtecan-nxki) has secured approval from the U.S. Food and Drug Administration (FDA) for treating adults with unresectable or metastatic hormone receptor (HR) positive, HER2 low, or HER2 ultralow breast cancer. This milestone expands treatment options for patients whose disease has progressed following endocrine therapies, further advancing precision oncology.

The approval is based on groundbreaking data from the DESTINY-Breast06 phase 3 trial, which demonstrated ENHERTU’s significant advantages over chemotherapy, including a longer progression-free survival (PFS) and higher response rates. This approval introduces the first HER2-directed therapy for patients with HER2 ultralow metastatic breast cancer, redefining care standards for this underserved population.

What Makes ENHERTU a Breakthrough Therapy for Metastatic Breast Cancer?

ENHERTU is a HER2-directed antibody-drug conjugate (ADC) that leverages Daiichi Sankyo’s proprietary DXd ADC technology. By targeting tumors with low or ultralow HER2 expression, it addresses a gap in treatment for HR-positive metastatic breast cancer patients who previously had limited options beyond chemotherapy.

The therapy demonstrated a median progression-free survival (PFS) of 13.2 months, significantly outperforming chemotherapy (8.1 months), with a 36% reduction in the risk of disease progression or death. In the HER2 low subgroup, ENHERTU achieved a confirmed objective response rate (ORR) of 62%, with 2.8% of patients showing complete responses and 59.2% achieving partial responses.

An exploratory analysis of HER2 ultralow patients further reinforced the therapy’s potential, with a median PFS of 15.1 months compared to 8.3 months for chemotherapy. This data underscores ENHERTU’s ability to redefine treatment outcomes for both HER2 low and HER2 ultralow populations.

How Does the DESTINY-Breast06 Trial Support ENHERTU’s Approval?

The DESTINY-Breast06 trial enrolled 866 participants with HR-positive, HER2 low, or HER2 ultralow metastatic breast cancer. Patients received either ENHERTU (5.4 mg/kg) or investigator-selected chemotherapy. The trial was pivotal in demonstrating the superiority of ENHERTU, particularly in chemotherapy-naïve patients, by significantly reducing disease progression risks and improving response rates.

Dr. Aditya Bardia, Program Director of Breast Oncology at UCLA Health, noted that ENHERTU’s median PFS of over a year, coupled with its robust ORR, marks a significant advancement. “Trastuzumab deruxtecan offers a potential new standard of care for patients with HR-positive metastatic breast cancer, especially those with HER2 low or ultralow expression,” Bardia explained.

The trial also highlighted the importance of precise HER2 testing. Central laboratory assessments reclassified nearly two-thirds of tumors initially labeled HER2 0 as HER2 low or ultralow, emphasizing the need for accurate diagnostic techniques to identify eligible patients.

Why Is This Approval a Turning Point for Breast Cancer Care?

ENHERTU’s approval broadens the scope of HER2-targeted therapies by including patients with ultralow HER2 expression, a group historically underserved by previous treatments. Experts believe this paradigm shift will pave the way for more personalized care in metastatic breast cancer.

Krissa Smith, Vice President of Education at the Susan G. Komen Foundation, emphasized the significance of these advancements: “Patients with tumors that are HER2 low or ultralow now have additional treatment options, enabling more personalized and informed decision-making alongside their healthcare teams.”

What Does the Approval Mean for Daiichi Sankyo and AstraZeneca?

The approval triggered a $175 million milestone payment from AstraZeneca to Daiichi Sankyo, underscoring the importance of their collaboration in advancing ADC technology. U.S. sales of ENHERTU will be recognized by Daiichi Sankyo, reinforcing its position as a global leader in oncology innovation.

ENHERTU is now approved in over 75 countries for various HER2-positive and HER2-low cancers, including metastatic breast cancer, non-small cell lung cancer (NSCLC), and gastric cancers. This approval extends the therapy’s reach, further solidifying its role as a cornerstone treatment across HER2-expressing cancers.

What Are the Safety Considerations for ENHERTU?

While ENHERTU offers substantial benefits, it comes with notable risks, including Boxed Warnings for interstitial lung disease (ILD) and embryo-fetal toxicity. In the DESTINY-Breast06 trial, common adverse reactions included fatigue, decreased white blood cell counts, nausea, and musculoskeletal pain.

Despite these risks, industry leaders remain optimistic about ENHERTU’s transformative potential. Ken Keller, CEO of Daiichi Sankyo, emphasized the therapy’s role in advancing care standards: “ENHERTU continues to redefine the classification and treatment of HR-positive metastatic breast cancer, offering new hope to patients who previously had limited options.”

ENHERTU Redefines HER2-Targeted Therapy

The FDA approval of ENHERTU for HER2 low and ultralow metastatic breast cancer represents a significant milestone in precision oncology. By addressing the unmet needs of this patient population, Daiichi Sankyo and AstraZeneca have set a new benchmark in HER2-targeted treatments.

As more patients gain access to ENHERTU, its approval underscores the importance of HER2 testing and the potential of innovative ADC therapies to transform cancer care.