Combination of eribulin and capecitabine provides clinical benefit for women with metastatic breast cancer

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Published: 12 Dec 2014
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Dr Chris Twelves - St James's Hospital, Leeds, UK

Dr Twelves speaks to ecancertv at SABCS 2014 about the results of a phase II study combining eribulin, a new mitotic inhibitor, with capecitabine in the treatment of metastatic breast cancer.

Results suggest that this therapy is effective in women with metastatic breast cancer, with a safety and tolerability profile consistent with previous data.

Read the news story here.

You have been studying, in the setting of metastatic breast cancer, a new approach, well it’s an approach that has recently been used elsewhere, but can you tell me what it was you were doing with this new compound, this new agent, eribulin?

Thank you, yes. This is an interesting new compound that’s been in development for some years and we’ve already presented very encouraging phase III data looking at eribulin in patients with heavily pre-treated metastatic breast cancer where we’ve clearly shown overall survival improvements which is really very unusual in this setting.

And that was the EMBRACE study; can you run me through the data on that because it is important?

Yes, that was a large study in patients with metastatic disease, all of whom had received an anthracycline and a taxane and they were randomly allocated either to the new drug, eribulin, or to whatever treatment the oncologist would have used under those circumstances.

And this new drug is a mitotic inhibitor, what does that do?

Yes, it’s a cytotoxic, similar in some ways to other agents such as the taxanes and the vinca alkaloids in that it targets the microtubule but it does so in a quite distinct and different way. It’s also unusual in being a natural product, it was extracted originally, although the parent compound was extracted, from a marine sponge off the coast of Japan.

Now what were you trying to do in this new study that you’re presenting here at the San Antonio Breast Cancer Symposium?

This new study built on the results of those two large phase III studies which had shown the benefits of eribulin in patients with metastatic disease and looked to see whether we could combine what is now one of the leading drugs in treating metastatic disease, eribulin, with another of those leading drugs, capecitabine.

So previously in monotherapy it was shown to have an advantage; you’ve now tried it with capecitabine, tell me about the study please.

Yes, in general for patients with metastatic breast cancer we generally do prefer sequential use of single agents because in the past most combinations of the more active single agents, when they’ve been put together, we’ve usually seen some increase in response rates but at the expense of a significant increase in toxicity with little, if any, impact on survival. So we were combining eribulin and capecitabine, two of the premier cytotoxics for the treatment of metastatic breast cancer, and one thing that encouraged us was that they had very distinct and different side effect profiles as single agents. Eribulin can cause myelosuppression and neuropathy, neither of which are significant with capecitabine which can cause hand-foot syndrome and diarrhoea. That encouraged us to think we could use the two of them alongside each other in combination, hopefully without encountering undue toxicity.

Now this is in patients who have not been treated before?

This is in patients who had received, in most cases, two or three lines of prior treatment for their metastatic disease; they’d all received an anthracycline and a taxane in the past.

What did you get, what results?

We treated a total of 42 women; we saw very encouraging levels of activity in terms of the response rate, which was 43%. That’s a significant reduction in response according to the classical criteria. Interestingly we also saw an additional group of patients who had stabilisation of their disease for around six months or more. If we combine those two groups together, the objective response and that prolonged stable disease, we have a clinical benefit rate of over 55%.

What about adverse events?

Adverse events were seen but they were essentially the adverse events that we would have expected from the individual agents. So, for example, we did see a high incidence of myelosuppression which is characteristic of eribulin but, as we’ve seen using it as a single agent, in the vast majority of patients that myelosuppression is asymptomatic with only a small proportion of patients developing febrile neutropenia.

So bearing in mind the fact that you were trying to get a more gentle therapy rather than a standard cytotoxic in this group of patients, were your hopes realised?

They were in that we achieved the sort of response rate that we were looking for with a much better tolerated regimen. It was also encouraging that the duration of response for that 42%, 43% of patients who responded was almost nine months. When we looked across the whole population of patients the median time to progression was over seven months.

What do you think doctors can take away from this in terms of how they should now be treating patients then?

I hope it will make doctors think again about combination chemotherapy and realise that we can combine two of the most effective single agents in a way that we do see the benefits in terms of efficacy, response rates and time to progression without unacceptable toxicity. I was fortunate more than ten years ago being part of one of the earlier trials that combined two very active agents in metastatic breast cancer where we added the drug docetaxel to capecitabine. Interestingly, with that combination we saw very similar response rates, very similar time to progression to what we see with eribulin and capecitabine. The difference is that patients really struggled with the combination of capecitabine and docetaxel; they had many more side effects, most of them couldn’t receive more than six cycles of treatment whereas with this combination of eribulin and capecitabine many, many patients were continuing for up to a year or even longer remaining on treatment.

So how would you summarise what doctors should take home from your findings, as presented here?

To think again about combination chemotherapy and be open to the possibility that we may indeed have a combination that is highly effective but not unduly toxic and that we perhaps should look again at the question of combination chemotherapy and its place in treating patients with metastatic disease.