Daiichi Sankyo and AstraZeneca are padding the case for their antibody-drug conjugate Enhertu with new data demonstrating the medicine’s worth in patients whose cancer has spread to the brain.
The partners unveiled positive results from the phase 3b/4 DESTINY-Breast12 study, which saw Enhertu chart substantial overall and intracranial clinical activity in a large clutch of patients with HER2-positive metastatic breast cancer who have brain metastases and received two or less lines of therapy in the metastatic setting.
The data on the antibody-drug conjugate (ADC) were simultaneously published in Nature Medicine and presented as a late-breaking presentation at the 2024 meeting of the European Society for Medical Oncology (ESMO) Friday.
The results won’t drive a new indication for Enhertu given that the drug’s current label doesn’t exclude patients with brain metastases. But data on those particular patients, which was previously limited, now add to a growing body of evidence around Enhertu’s merit.
On the trial’s primary progression-free survival (PFS) endpoint—which measures the time a patient lives without their disease getting worse—Enhertu yielded a 12-month PFS rate of 61.6% in patients with brain metastases at baseline, AZ and Daiichi said in a release. Further, patients with brain metastases showed a central nervous system (CNS) 12-month PFS rate of 58.9%.
The results were consistent across patients with stable and active brain metastases, the partners added.
Specifically, those with stable brain metastases achieved a 12-month PFS rate of 62.9% on Enhertu and a 12-month CNS PFS rate of 57.8%. Alternately, patients with active brain metastases had a 12-month PFS rate of 59.6% and a 12-month CNS PFS rate of 60.1%.
The 12-month PFS for patients with brain metastases in DESTINY-Breast12 was roughly in line with the 72% observed in an exploratory analysis of a small group of similar patients enrolled in DESTINY-Breast03 that got Enhertu its approval in previously treated HER2-positive breast cancer, the trial investigators noted in the Nature Medicine study.
Being able to show some CNS activity could help Enhertu in its competition with Pfizer’s small-molecule drug Tukysa, which was obtained in the New York pharma’s acquisition of Seagen.
In the phase 2 HER2CLIMB study conducted in patients with heavily pretreated HER2-positive breast cancer, Tukysa's combination with chemo and trastuzumab delivered a median CNS PFS of 9.6 months in patients with active brain metastases, or 13.9 months in those with stable brain metastases.
Up to 50% of patients with HER2-positive metastatic breast cancer see their disease spread to the brain over time, in turn significantly impacting quality of life and disease outcomes, Dana-Farber’s Nancy Lin, M.D., who served as the principal investigator for DESTINY-Breast12, pointed out in a statement.
“Treating brain metastases in patients with breast cancer is challenging as there are few effective treatment options,” Mark Rutstein, global head of oncology development at Daiichi, said in a separate statement. “Building on previous studies, these results show Enhertu can provide strong overall and intracranial clinical activity and support its potential role in treating patients with active or stable brain metastases.”
The data boost comes as Enhertu's sales growth has slowed down in recent months. In July, Daiichi and AZ reported combined Enhertu sales of $893 million for 2024’s second quarter, reflecting a scant 1.6% sequential increase from the first three months of the year.
Even still, AZ’s oncology business chief Dave Fredrickson at the time said the British drugmaker expects Enhertu to return to “more robust sequential growth” in the second half of the year.
Enhertu is one of six marketed products that AZ expects could reach more than $5 billion in global sales at peak.