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The first trial to prove a drug helps HER2-positive brain metastases, extending survival by four and a half months overall.
HER2CLIMB, trial NCT02614794 sponsored by Seagen, now Pfizer, and reported in 2019, was the first trial to prove that a drug helps HER2-positive brain metastases, extending survival overall and in patients with brain disease. It randomised 612 women with HER2-positive metastatic breast cancer after trastuzumab, pertuzumab and trastuzumab emtansine, including 48 percent with active brain metastases, to tucatinib or placebo with trastuzumab and capecitabine, met its primary progression-free survival endpoint, improved overall survival and sharply reduced central nervous system progression, leading to approval in April 2020. OnCo links it to HER2 as a target, tucatinib, trastuzumab, the HER2-positive brain metastases term, Nancy U. Lin and the brain as a bottleneck. Whether systemic therapy should now come before local brain treatment is the open question.
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.
612 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survivalprimary | Tucatinib arm | 320 | 7.8 months | 0.54 (0.42 to 0.71) | <0.001 | link |
| Placebo arm | 160 | 5.6 months | ||||
| Overall survival | Tucatinib arm | - | 21.9 months | 0.66 (0.5 to 0.88) | 0.005 | link |
| Placebo arm | - | 17.4 months |
This analysis is the evidence base for treating active HER2-positive brain metastases with a systemic regimen, sometimes deferring radiotherapy, and for tucatinib's brain-specific labelling.
Tucatinib-based therapy is the standard for HER2-positive disease with active brain metastases and a standard later-line option overall; it was the first trial to enrol progressing brain metastases and show a systemic drug helps them.
Shares HER2 tyrosine kinase inhibitors, HER2-positive breast cancer with brain metastases, Tucatinib, Pfizer (incl. Seagen).
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 HER2 tyrosine kinase inhibitors, HER2-positive breast cancer with brain metastases, Tucatinib, Pfizer (incl. Seagen).
Shares HER2 tyrosine kinase inhibitors, Tucatinib, Pfizer (incl. Seagen), Trastuzumab.
Shares HER2 tyrosine kinase inhibitors, Tucatinib, Pfizer (incl. Seagen), Trastuzumab.
Shares HER2 tyrosine kinase inhibitors, Tucatinib, Pfizer (incl. Seagen), Trastuzumab.
Shares HER2CLIMB: tucatinib with trastuzumab and capecitabine for HER2-positive metastatic breast cancer, including brain metastases, HER2-positive breast cancer with brain metastases, HER2-positive breast cancer.
Shares HER2 tyrosine kinase inhibitors, Tucatinib, Pfizer (incl. Seagen), HER2-positive breast cancer.