Systemic therapy for central nervous system metastases

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Published: 19 Jan 2011
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Dr Nancy Lin - Dana-Farber Cancer Institute, Boston, USA
Nancy Lin discusses the session she chaired at the 2010 San Antonio Breast Cancer Symposium on metastases in breast cancer, and specifically her talk on trying to tackle cancer that has spread to the central nervous system by chemotherapy and targeted therapies. Also taking into account the type of breast cancer, e.g. HER 2 positive or triple negative and the life expectancy. Patupilone and ANG1005 are also used to cross the blood brain barrier, increasing efficacy of treatment.

2010 San Antonio Breast Cancer Symposium, 8-12th December, USA


Interview with Dr Nancy Lin (Dana-Farber Cancer Institute, Boston, USA)


Systemic therapy for central nervous system metastases

I chaired a session regarding CNS metastases from breast cancer and it was a session where we had a series of speakers related to different areas in brain metastases research, specifically neurosurgical techniques, radiation therapy, systemic therapy and then pre-clinical and translational approaches. The session, I was very gratified to see how well attended it was and I think it just speaks to the fact that we don’t have very much to offer patients besides the standard therapy of radiation and surgery. It’s an area that’s of increasing interest to both clinicians and also patients because of the improvements in systemic therapy that have led to longer survival in patients with metastatic breast cancer but many of the standard chemotherapies don’t adequately get into the brain.


What was your talk about?


The talk that I gave was regarding systemic therapy for brain metastases and specifically looking at chemotherapy and targeted therapies. I first discussed what has changed in terms of the prognosis of patients with brain metastases, so in historical series the estimates are that somebody might have six months on average median survival after a diagnosis of brain metastasis from breast cancer but more recent data has indicated that there is a lot of difference according to breast cancer subtype.


So for patients who have HER2 positive breast cancer, many series have now reported median survival of one to two years which is obviously substantially longer than six  months, whereas for triple negative patients the survival is still less than six months. So this difference really speaks to differences in the biology between the two different breast cancer subtypes but also has a lot of implications in terms of how we treat our patients because you might imagine that for somebody in whom you expect their life expectancy to be less than six months you might offer different options and have a different approach to their care than somebody whose prognosis is in the one to two year range.


The other thing that I talked about was specific systemic therapies, especially clinical trials that are going on in this area. So we talked a little bit about some chemotherapies that are being developed that actually cross the blood-brain barrier very well in contrast to many of the other chemotherapies that are out there right now. We also talked about a number of categories of systemic therapies, so we talked about HER2 directed therapies, reviewed a little bit of the Lapatinib data but also discussed some of the on-going and planned trials with other tyrosine kinase inhibitors. We discussed angiogenesis inhibitors and then we discussed PARP inhibitors.


Which chemotherapies?


In terms of chemotherapy, two that I specifically discussed were one called Patupilone, which is an epothilone that crosses the blood-brain barrier and a study has been completed, a phase II study, where there were some responses seen in patients. I think that’s probably a reasonable building block for other regimes potentially combining it with targeted therapies.


I also discussed a compound called ANG1005 which is Paclitaxel conjugated to Angiopep-2 and what this does, it actually allows the compound to cross very well into the brain. There have been a fairly substantial number of responses actually in a phase I study of refractory brain metastases patients. So there’s definitely a lot of interest in taking that to phase II and beyond.


Given the difficulty of treatment in this area, what should we be positive about?


One is just that for the HER2 positive patients, that’s one area where on the one hand the negative, of course, is that there are a substantial number of metastatic patients who develop this problem, but on the positive side the survival certainly is much better than it was ten or fifteen years ago, so I think that’s good.


There are a number of agents that are being looked at in this setting, including Lapatinib based combinations including Neratinib or HKI272 including angiogenesis inhibitors. So the positive from that standpoint is the fact that this is an increasingly recognised area, there actually are trials that are happening in this space now where there were very few trials before and I hope that this is going to lead to improvements in care.


For triple negative patients much of the excitement, not just for CNS disease but in general, has been around the PARP inhibitors and there is actually a PARP inhibitor trial for brain metastases currently on-going and CNS is one of the sites that is going to be specifically looked at in some of the PARP trials that are not related to CNS disease because it’s such an important issue for triple negative breast cancer.


What is the PARP inhibitor trial for brain metastases called?


That’s a trial with the BSI201 compound in combination with the chemotherapy Irinotecan and that’s being led by Dr Carrie Anders at UNC and actually will be open across a number of sites across the US; that will be a phase II trial. That’s currently already open at UNC but will soon open at other sites.[