ESMO: AZ and Daiichi support Enhertu for breast cancer patients with brain metastases

Daiichi Sankyo and AstraZeneca have released new data supporting their antibody-drug conjugate, Enhertu, highlighting its effectiveness in treating patients with metastatic breast cancer that has spread to the brain. The results, derived from the phase 3b/4 DESTINY-Breast12 study, demonstrate significant overall and intracranial clinical activity in patients with HER2-positive metastatic breast cancer and brain metastases who have undergone two or fewer lines of therapy. This new data adds to the growing body of evidence supporting Enhertu's capabilities.

The study's primary endpoint focused on progression-free survival (PFS), which measures the duration a patient lives without the disease worsening. Enhertu achieved a 12-month PFS rate of 61.6% in patients with brain metastases at baseline. Moreover, the central nervous system (CNS) 12-month PFS rate for these patients was 58.9%. These results were consistent across patients with both stable and active brain metastases.

Patients with stable brain metastases treated with Enhertu showed a 12-month PFS rate of 62.9% and a CNS PFS rate of 57.8%. For those with active brain metastases, the 12-month PFS rate was 59.6%, and the CNS PFS rate was 60.1%. The PFS observed in DESTINY-Breast12 aligns closely with the 72% seen in a smaller group of patients in the DESTINY-Breast03 study, which played a role in Enhertu's approval for previously treated HER2-positive breast cancer.

Demonstrating CNS activity is crucial for Enhertu as it competes with Pfizer’s Tukysa, another treatment for HER2-positive breast cancer. In the phase 2 HER2CLIMB study, Tukysa, combined with chemotherapy and trastuzumab, showed a median CNS PFS of 9.6 months for patients with active brain metastases and 13.9 months for those with stable brain metastases.

Up to 50% of patients with HER2-positive metastatic breast cancer eventually experience brain metastases, significantly affecting their quality of life and disease outcomes. Nancy Lin, M.D., the principal investigator for DESTINY-Breast12 from Dana-Farber, emphasized the challenge in treating brain metastases in these patients due to limited effective treatment options. Mark Rutstein, global head of oncology development at Daiichi, stated that these results build on previous studies and show that Enhertu offers strong overall and intracranial clinical activity, supporting its potential role in treating patients with either active or stable brain metastases.

Despite the promising data, Enhertu's sales growth has recently slowed. In July, Daiichi and AstraZeneca reported combined sales of $893 million for Enhertu in the second quarter of 2024, reflecting a modest 1.6% increase from the first quarter. However, Dave Fredrickson, AstraZeneca’s oncology business chief, expressed optimism, predicting a return to “more robust sequential growth” in the latter half of the year.

Enhertu stands out as one of six marketed products that AstraZeneca expects could achieve over $5 billion in global sales at peak, reinforcing its significant potential in the oncology market.