By: Greg Laub
— Updated results show 9-month survival benefit in those with active or untreated brain metastases
At the virtual San Antonio Breast Cancer Symposium, researchers presented new data from an exploratory analyses from the pivotal HER2CLIMB trial. After an additional 15.6 months of follow-up, the overall survival (OS) benefit when tucatinib (Tukysa) was added to trastuzumab (Herceptin) and capecitabine was maintained for patients with HER2-positive metastatic breast cancer who had stable or active brain metastases.
So at San Antonio this year I presented the updated results of the HER2CLIMB brain metastasis subset. And this is now based on about 29.6 months of follow-up data. So longer follow-up than what had been seen in the previous presentations.
This presentation focuses on the subset of 291 patients with brain metastases enrolled in the HER2CLIMB trial. And importantly, 174 of those patients had active or untreated brain metastases entering the clinical trial, which is really quite different from most other trials in breast cancer.
With the updated data, I think the most impressive finding is the survival data. So if we look at all patients with brain metastasis, the median overall survival was 12.5 months in the placebo arm compared to 21.6 months in the tucatinib arm. So that’s a more than 9-month improvement in absolute overall survival in this patient population with a hazard ratio of 0.6. The previous estimates were 12 versus 18 months, but with additional follow-up, we’re actually seeing the survival curves split even further.
If we look at the subset of patients who have active brain metastases, the overall survival similarly went from about 12 months to 21 months — again, hazard ratio of 0.52. And remember, these are patients with active brain metastases, progressive after THP [docetaxel, trastuzumab, pertuzumab (Perjeta)] and T-DM1 [ado-trastuzumab emtansine (Kadcyla)]. So a very heavily pretreated population. Really, I think, an unprecedented 9-month survival advantage in an active brain mets population. And then if we look at the patients with stable brain metastases, again a survival differential was seen. The absolutes were 16.4 months versus 21.6 months.
The other thing that was important was the follow-up of the time to CNS [central nervous system] progression. So the CNS progression-free survival [PFS] was also significantly better with tucatinib. The hazard ratio there was 0.38. And that was true both in the patients with active brain metastases as well as those patients with stable treated brain metastases. So there’s certainly some discussion about what we should do best for patients with stable treated brain metastases. But I do think that the CNS-PFS data is very compelling. In those patients with stable treated brain mets, the median CNS-PFS went from 5.6 out to 13.9 months. So really quite impressive data. And finally the response data in the CNS was confirmed as well as the duration of response being nearly three times longer with tucatinib as compared to the placebo group.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.