In your head

Top Line: HER2CLIMB showed a very encouraging rate of intracranial activity for the small molecule HER2-TKI tucatinib for women with late-stage HER2+ breast cancer. 
The Study: This study takes an exploratory look at outcomes for the 48% of enrollees with brain metastases. As a reminder, they had progressive disease after previously receiving trastuzumab, pertuzumab, and T-DM1 and were randomized to receive tucatinib or placebo along with capecitabine and trastuzumab. Among these 291 women, 60% had active (new or progressing) brain mets at enrollment, while the rest had stable, previously treated brain mets. At 1 year, the rate of CNS progression-free survival (CNS-PFS) was 40% with tucatinib...versus 0% without. Tucatinib more than doubled median CNS PFS from 4 → 10 months, even achieving a marked improvement in 1-year overall survival from 47 → 70%. For the subset of women with active brain mets, median OS was nearly doubled from 12→ 21 months. And while it might be tempting to go it alone with tucatinib in the brain, these patients had very frequent brain MRIs. And in those who received focal radiation for progression while staying on tucatinib, the median time to a second event was over 8 months. 
TBL: Tucatinib when combined with trastuzumab and capecitabine has significant intracranial activity for women with HER2+ brain met after prior HER2-targeted therapy. | Lin, J Clin Oncol 2020


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