medwireNews: Tucatinib, a selective HER2 kinase inhibitor, added to trastuzumab and capecitabine has demonstrated a survival benefit in patients with HER2-positive breast cancer and brain metastases in the HER2CLIMB trial, as presented at the virtual 2020 ASCO Annual Meeting.
Presenting author Nancy Lin (Dana-Farber Cancer institute, Boston, Massachusetts, USA) explained that the tucatinib in combination with trastuzumab and capecitabine, previously exhibited superior survival to placebo in heavily pretreated women with metastatic breast cancer, including, but not exclusively, patients with brain metastases, in the phase 2 part of the HER2CLIMB trial.
The current analysis, which was simultaneously published in the Journal of Clinical Oncology, focused on 291 participants from the original HER2CLIMB study population, all of whom had brain metastases at baseline.
Presenting author Nancy Lin discusses the HER2CLIMB trial (5:12).
For the 198 patients who were randomly allocated to receive tucatinib, Lin said they observed a significant 68% reduction in central nervous system (CNS) progression-free survival (PFS) compared with the 93 patients who received placebo, with a respective CNS PFS duration of 9.9 months versus 4.2 months.
Furthermore, tucatinib-treated patients had a 42% reduced risk for death, with a median overall survival of 18.1 months versus 12.0 months for placebo-treated patients.
In total, 174 patients had an active brain metastasis at baseline and 117 had stable brain metastases. In both patient populations tucatinib significantly reduced the risk for intracranial progression or death, by 64% and 69%, respectively, compared with placebo. The median PFS duration was 9.5 months and 13.9 months among tucatinib-treated patients with active and stable brain metastases, respectively, while the corresponding durations were 4.1 months and 5.6 months for placebo-treated patients.
Lin reported that the confirmed intracranial objective response rate among the 75 patients who had active brain metastases and measurable intracranial lesions at baseline was higher, albeit not significantly, among the 55 patients in the tucatinib group, at 47% versus 20% for the 20 patients in the placebo group.
And the confirmed duration of intracranial response was 3.8 months longer for patients who received tucatinib than those given placebo (median, 6.8 vs 3.0 months), but again this was not significant.
During the study period, 30 patients experienced an isolated brain progression and continued to receive the study therapy in addition to local treatment directed at the CNS. Among 21 of these patients who received tucatinib, the risk for a second progression or death was reduced by a significant 67%, compared with placebo, with a median PFS duration – from baseline – of 15.9 versus 9.7 months.
“These data suggest a potential benefit for continuation of tucatinib beyond first isolated CNS progression,” said Lin.
And she concluded that “these results, together with the HER2CLIMB primary analysis demonstrate that the triplet of tucatinib, trastuzumab, and capecitabine is an active regimen for intracranial and extracranial disease in patients with HER2-positive metastatic breast cancer.”
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2020 ASCO Annual Meeting; 29-31 May
J Clin Oncol 2020; doi:10.1200/JCO.20.00775