ENHERTU® Shows Major PFS Benefits in HR+, HER2-Low Metastatic Breast Cancer Post-Endocrine Therapy in DESTINY-Breast06 Phase 3 Trial

The phase 3 DESTINY-Breast06 trial has yielded positive results, showing that ENHERTU® (trastuzumab deruxtecan) significantly improved progression-free survival (PFS) in patients with hormone receptor (HR) positive, HER2 low metastatic breast cancer. This improvement was observed after one or more lines of endocrine therapy, which is standard for such patients. The drug demonstrated its efficacy in both the primary patient group and the overall trial population, which included those with HER2 low and HER2 ultralow metastatic breast cancer.

ENHERTU, a HER2-directed antibody-drug conjugate (ADC), is a product of Daiichi Sankyo and AstraZeneca's collaboration. It has shown an early trend towards overall survival (OS) improvement in the trial's patients with HER2 low metastatic breast cancer. Although OS data were not mature at the time of analysis, the trial will continue to assess this and other secondary endpoints.

Approximately 60% to 65% of HR positive, HER2 negative breast cancers are considered HER2 low, with an additional 25% potentially being HER2 ultralow. Traditional endocrine therapies are commonly used for early treatment stages of HR positive metastatic breast cancer, but their effectiveness is often limited after two lines of treatment. The current standard of care post-endocrine therapy is chemotherapy, which is known for its poor response rates and outcomes.

The results of the DESTINY-Breast06 trial suggest that ENHERTU could set a new standard of care for patients with HER2 low and HER2 ultralow metastatic breast cancer following endocrine therapy. The safety profile of ENHERTU was consistent with previous trials, with no new safety concerns identified.

The findings from the DESTINY-Breast06 trial will be presented at an upcoming medical conference and will be shared with global regulatory authorities for review. The trial itself is a global, randomized, open-label phase 3 study that enrolled 866 patients across multiple regions, including Asia, Europe, North America, and South America.

Breast cancer is a leading cause of cancer-related deaths worldwide, with over two million cases diagnosed in 2022 and more than 665,000 deaths globally. HR positive, HER2 negative is the most common breast cancer subtype. Historically, tumors not classified as HER2 positive were considered HER2 negative, but many of these still exhibit some level of HER2 expression.

ENHERTU has been approved in numerous countries for the treatment of various types of cancer, including HER2 positive breast cancer, HER2 low breast cancer, and non-small cell lung cancer (NSCLC) with activating HER2 mutations. It is also approved for HER2 positive gastric or gastroesophageal junction adenocarcinoma, and for HER2 positive solid tumors that have received prior systemic treatment.

A comprehensive clinical development program is underway to evaluate the efficacy and safety of ENHERTU as a monotherapy and in combination with other anticancer treatments across multiple HER2 targetable cancers. Daiichi Sankyo and AstraZeneca are also collaborating on the development of other ADCs, such as datopotamab deruxtecan and patritumab deruxtecan, among others.

ENHERTU's U.S. safety information includes warnings for interstitial lung disease and embryo-fetal toxicity. It advises monitoring for respiratory symptoms and the use of effective contraception during treatment due to potential risks to a fetus. There are no contraindications listed for ENHERTU, but additional precautions are advised for conditions such as neutropenia and left ventricular dysfunction.