The study was a very simply designed and pragmatic one. Actually, the first line option is a combination of taxanes with bevacizumab in patients that are candidates to receive chemotherapy. So for those patients we know that after some cycles it’s sometimes difficult to maintain the taxane treatment so when we stop the taxane treatment and we don’t have any progression we’re continuing just with bevacizumab. The trial addresses the question of comparison of what is the standard maintenance, bevacizumab, versus maintenance with the addition of capecitabine after stopping the taxane.

So the basic idea is can you remove the taxane and use capecitabine which should be a relatively gentle drug instead.

Exactly. Less toxicity potentially but also a non-cross resistant drug that means that maybe we will have also an amplified benefit regarding the fact that we are introducing a switch maintenance affording the patient the possibility to have better outcomes.

Potentially very interesting then. How many patients did you look at and what did you see?

Clearly we have included 300 patients, among them 200 have benefit from the first phase of taxanes with bevacizumab combination and those patients were randomised between two possibilities: bevacizumab alone or bevacizumab in combination with capecitabine. The primary endpoint was progression free survival from the maintenance initiation. The results we found clearly are strong positivity regarding the PFS. We have three times more controlled disease with capecitabine bevacizumab compared to bevacizumab alone. The PFS for those patients that have received capecitabine with bevacizumab in the maintenance phase is close to 17 months; that means approximately one year and a half compared to a little bit less than one year just with bevacizumab maintenance.

So you’re getting a big difference, what about the difference in toxicities?

Yes. If you look at the toxicity there is an increasing rate of toxicity for the patients that have been exposed to capecitabine with about 30% hand-foot syndrome, this is the main issue. But in fact we have also looked at the general quality of life statements from the patients and this was published actually in Lancet Oncology showing that there is no difference regarding this point. So there is a little bit more toxicity but clearly the impact on PFS is so strong that it’s limited regarding the quality of life impact.

It is, of course, dangerous to talk about the impact on overall survival but what are your thoughts?

We have a positive trial on overall survival because we have looked exactly on the overall survival and the hazard ratio is 0.38 with an increase of more than one year difference regarding the overall survival benefit. So actually looking at the results of the trial, looking at the PFS and the improvement of overall survival there is a clear, strong signal that first maintenance treatment is an important issue, the quality of the maintenance you give to the patient, and the strategy regarding this maintenance in metastatic breast cancer. For those patients who are beginning the treatment with taxanes and bevacizumab, having a switch on maintenance to capecitabine bevacizumab might clearly improve PFS and strongly overall survival.

So it sounds that you… you say you’ve got a hazard ratio less than a half in overall survival.

That’s true.

And that’s statistically significant too?

Yes.

So it’s a done deal and you should all switch to capecitabine?

It’s just one trial. You know that sometimes, let’s say, that the clinicians are very cautious with the results but I have to confess that it is the first time for a long time that in the HER2- population we have a positive trial in overall survival that clearly addresses the question of this strategy as possibly a standard of care and also for the future the way we will define and think about the way to treat the patient with the maintenance treatment.

What, very briefly then, is the take home message that doctors should take away from your findings?

I will say that for those patients for whom we are initiating the treatment with bevacizumab and taxanes clearly decide and also design the strategy that you will use for treating those patients. After a short phase of induction with bevacizumab and taxanes, if the patients do not have progression switching to capecitabine and bevacizumab may clearly be, for me, the standard of care.