ESMO 2012

Putting drugs to work against brain metastases in HER2 positive breast cancer: LANDSCAPE study

Dr Thomas Bachelot – Centre Leon Berard, Lyon, France



You’re the lead investigator on the LANDSCAPE trial and you presented some very interesting data yesterday. Can you summarise these for us?

Yes, the LANDSCAPE study was done to assess the potential efficacy of a combination of lapatinib and capecitabine in front line treatment of brain metastases from HER2 positive metastatic breast cancer patients. The idea behind that was that, first, this combination of lapatinib and capecitabine has been shown to be efficient for patients progressing after radiotherapy, first. Then, it has been showed that chemotherapy could be quite active for brain metastases before radiotherapy in other types of breast cancer. So we decided to use this combination in front line in order to delay, if possible, the whole brain radiotherapy because whole brain radiotherapy is quite toxic and it can include neurological toxicity with a decrease in neurocognitive function. So it could be a problem for those patients that will live for two years, something like that. So we decided to test this combination before neuroradiotherapy to delay the radiotherapy, first, and secondly to be able to treat both the brain metastases and the extra brain disease at the same time, so not to lose time for patients that have active systemic disease in the liver and so on.

So we included 45 patients, 44 were evaluable for efficacy and we had a very good response rate of 65% in the volumetric response rate. So it was quite a nice result. Only 7 patients did not respond to this treatment, all the other patients either had a very good partial response or a disease stabilisation. Then the median time to radiotherapy was 7.9 months so that’s quite consequent and that’s important for those patients, that I told you they have an overall survival that is between one and two years. So if you can postpone whole brain radiotherapy for 8 months, that will be all that time they won’t have the toxicity, most particularly the neurological toxicities of radiotherapy.

But all patients eventually have to have radiotherapy, or some?

Almost all had to have a little bit at one point; when it progressed, they almost all have. A few patients did not have it because they had other chemotherapy to do and the investigator was not keen to give radiotherapy but I think maybe one or two only. All the patients at one point will have radiotherapy. There was another point I wanted to discuss here rapidly. There was a sub-study we made with the analysis of circulating tumour cells disease at the start of treatment and then at 21 days after beginning the treatment. We have some very nice results here with regard to predictive and prognostic value of CTCs for this subgroup of patients. So that will be the subject of a specific publication that we are currently writing.

OK, so you can’t speak about the results?

Yes, I can speak a little bit, you see it’s very interesting. For example, the patient with at least one CTC at diagnosis had a median overall survival of one year, roughly. We cannot say overall median survival because it’s too early but the time at one year 50% of the patients were alive and, by contrast, the patients with no CTCs at diagnosis, 80% of them were alive at one year. So that is a huge difference that is very significant. For the whole population the overall survival is 17 months, that is consistent with what has been published with radiotherapy alone. So, in conclusion, our study shows that in terms of response rate and overall survival, the result of front line chemotherapy and lapatinib is equivalent to what has been published with whole brain radiotherapy and could delay radiotherapy. The CTC analysis may be of high interest for predictive value. This study will be published in Lancet Oncology at the end of the year, it has been accepted already.

OK, thank you.

You’re welcome.