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Enhertu shrank brain metastases in most patients, including those with untreated lesions, answering a question its earlier trials had excluded.
DESTINY-Breast12, trial NCT04739761 sponsored by AstraZeneca and Daiichi Sankyo and reported in 2024, was a phase 3b/4 single-arm study showing that trastuzumab deruxtecan shrinks brain metastases in most patients with HER2-positive metastatic breast cancer, including those with untreated lesions, answering a question its earlier trials had excluded. Among 504 patients, 263 with brain metastases, the intracranial objective response rate was high, higher still in active or untreated brain metastases, and most patients with brain disease were progression-free at twelve months. OnCo links it to trastuzumab deruxtecan, the HER2-positive brain metastases term, the idea of systemic-first management of brain metastases and the brain as a bottleneck. Without a randomised comparison, whether systemic therapy should replace radiotherapy first in selected patients remains open.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
506 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Intracranial objective response rateprimary | T-DXd (brain metastasis cohort) | 263 | 71.7% | - | - | link |
Shares Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads), AstraZeneca.
Shares Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads), AstraZeneca.
Shares Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads), AstraZeneca.
Shares Systemic-first management of HER2-positive brain metastases, HER2-positive brain metastases, HER2-positive breast cancer with brain metastases, Brain metastases (secondary brain tumours).
Shares Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads), AstraZeneca.
Shares HER2-positive breast cancer with brain metastases, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads), HER2-positive breast cancer.
Shares Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads), Antibody-drug conjugate (ADC).
Shares Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads), Antibody-drug conjugate (ADC).