You’ve been looking at this agent, eribulin, and looking at it in a particular category of patients with breast cancer. What was it that you were trying to investigate? What was the big issue here?

Once we knew the activity of eribulin in metastatic breast cancer and once we knew the great activity in terms of overall survival we wanted to study the role of eribulin in naïve patients, in patients with primary tumours, HER2 negative primary tumours, to see if the activity observed in the metastatic setting was also observed in primary tumours.

And what exactly is special about eribulin?

Eribulin is an anti-microtubule agent which has shown again improved survival but it has also at least two or three different mechanisms of action which are very important indeed. One of them is that it can revert the so-called epithelial mesenchymal transition phenotype into the mesenchymal epithelial transition phenotype. Basically, it transforms the mesenchymal like phenotype into the epithelial like phenotype.

Does this make the cancer less aggressive then?

Exactly, it has two important consequences. One of them is that the capacity of these tumours to emigrate and to produce metastases is much lower once they have been transformed into the epithelial phenotype.

And in theory what’s the optimum way of using eribulin?

At the present time what we know is that eribulin is approved for the treatment of late line metastatic breast cancer in many countries but also in some countries, including Europe, it is approved in second line or beyond.

So potentially it could go into first line treatment?

Potentially it might go. There are some ongoing clinical trials to see that but in fact with the data we have today with this transformation into the more aggressive to the less aggressive subtype, I think that the best way to optimise the treatment with eribulin should be today in the second line much better than in the third line, much better than in the fourth line.

And it could help to sensitise tumours to other drugs?

That’s a very good point. Absolutely, yes. So with the study we have presented at San Antonio 2015 we have observed that we might transform the luminal B into the luminal A subtype. It could be very interesting to explore the role of eribulin with endocrine therapy because maybe we might sensitise these tumours to endocrine therapy.

That sounds a great hope, so tell me what you did in this study.

Basically what we wanted to observe is the activity of eribulin single agent before surgery in primary tumours in HER2 negative patients. We had two different cohorts, one of them is in ER positive HER2 negative patients and the other one in triple negative patients. So what we have presented so far is the ER positive HER2 negative cohort and we have observed first that eribulin works, eribulin has activity in this group of patients. But also, which I think is much more interesting, is that we have observed that luminal B tumours, 50% of them, are transformed, are changed into the luminal A tumours. I think this might have important consequences because we have decreased the aggressiveness of these tumours.

How well established is this? What was the size of the study and how sure are you that this remarkable transformation might be taking place?

The study was designed to include 200 patients in total, 100 with ER positive, 100 with triple negative. Again, we have presented only the ER positive cohort so we have included about 100 patients more or less. So I think that is an important number of patients to have demonstrated this change to the behaviour of these tumours. Again, this correlated very well with the data we had in the metastatic setting of certainly an improvement in survival.

What can you say in concrete terms about clinical implications and what can you say might happen clinically?

It has two clinical implications: one of them the aggressiveness of the tumours is much lower so clearly the expected outcomes seem to be better. This is something that has not been demonstrated in primary tumours but it should be. The second consequence is that it helps us to understand what we have observed in the metastatic setting, maybe we have improved survival because the tumour aggressiveness is better, is lower.

So how do you see this agent being included, say at the beginning on initial diagnosis in early breast cancer? From that point onwards how do you see eribulin being included?

Unfortunately there are not so many clinical trials in primary tumours today so we need usually thousands of patients so it’s difficult to understand this in that setting. I don’t know if this will open as a new opportunity to explore the drug in this setting, this is something we have to discuss in the future. But clearly, clearly, the behaviour of the tumour is different, that’s very important. So this agent might sensitise the tumour cells to be treated with endocrine therapy in the future.

So what should doctors be taking home from your findings about eribulin so far?

It might help a physician to understand why eribulin improves survival. So what I think is very important that based on this data I feel very comfortable in using eribulin in the metastatic setting as early as possible. So with this data I would try to use eribulin in second line in Europe.