ASCO 2012

ASCO 2012: Advances in metastatic castration-resistant prostate cancer; first-line cabazitaxel

Dr Stéphan Oudard – Hôpital Européen Georges Pompidou, France interviewed by Dr Chris Parker – Royal Marsden Cancer Centre, London, UK


Hello, I’m Chris Parker from the Royal Marsden and I’m speaking to you in Chicago from the ASCO 2012 annual meeting. I’m pleased to be joined now by Stéphan Oudard from Paris. Stéphan, you’re presenting an abstract here about a new trial, can you tell us about it?

Yes, of course. The trial is called the FIRSTANA trial, it’s a trial which is going to compare in the metastatic CRPC patient the impact or the efficacy of cabazitaxel compared to docetaxel in the first line setting, so chemo-naïve patient. As you know, we have published the TROPIC trial which looked at cabazitaxel in second line after docetaxel and at that time cabazitaxel was compared to mitoxantrone and showed a survival advantage compared to this old chemotherapy, I would say. This drug seems to be really active and maybe more active than docetaxel and have maybe less neuropathy and maybe has quite a high frequency of neutropenia but it seems that the drug by itself is really active. So that’s why we wanted to move to first line, in order to see whether the drug is as active or even more active than docetaxel and with maybe the same toxicity profile.

So what makes you think it might be more active than docetaxel? Have you got some data to support that?

Yes, because in the TROPIC trial those patients were resistant to docetaxel and we could know the resistance and we could have a good objective response, good tumour shrinkage and we know also that this drug may pass the brain-blood barrier so maybe in order to avoid brain metastases it could be useful. So this is my feeling about this drug.

Moving on then to the toxicity, some people seem to be a bit worried about the toxicity of cabazitaxel, they’re aware that there were some toxic deaths on the TROPIC trial. So what are your thoughts about how the toxicity compares between the two drugs?

Yes, you’re right. At the beginning of the TROPIC trial some patients had neutropenia and diarrhoea inducing death but after IDMC, they said that we need to prescribe GMCSF and to try to avoid diarrhoea and so on. After that we had no more toxic deaths and if you are aware about this supportive care you don’t face these kinds of problems. For now if you use cabazitaxel you need to use GCSF in order to prevent neutropenia. So this is the first point and now in the FIRSTANA trial in first line patients need to receive after the first cycle for this cycle two to cycle ten, for instance, cabazitaxel and GCSF to prevent neutropenia. So I would say that in the TROPIC trial the toxicity was maybe high but those patients were highly pre-treated and they had radiation therapy, a lot of cycles of chemotherapy, maybe that’s why they had so many side effects. I think that moving now to first line we will have the same range of side effects between cabazitaxel and docetaxel.

And in FIRSTANA you’re not just comparing the two drugs against each other, you’re also comparing two different doses of cabazitaxel.

Yes, that’s right.

Can you explain the rationale for that?

Yes. We think that maybe we have two different dosages, either 25 or 20mg/m2, the question is whether or not maybe by using the lower dose we will have the same efficacy and, by the way, decreasing the toxicity. So in the two phase I study we could have the choice between 20 or 25, I don’t know why we have chosen 25 in the TROPIC trial and we saw that due to the neutropenia frequency we may have to use a lower dose in the first line setting. So we will see if at the 20mg/m2 the drug is very active with low toxicity, I think dosage will be chosen in the future.

And just from your clinical experience so far, do you think there is going to be a big difference in toxicity between the two doses?

I think so, in terms of neutropenia I’m sure about that but diarrhoea I think is maybe more related to radiation therapy and other comorbidities, but neutropenia for sure.

And are you at all worried about any on-going docetaxel combination trials? Supposing that this year or next year we find that docetaxel alone is no longer standard of care but it’s docetaxel plus something else, do you think that’s a problem for you?

So far we didn’t have this kind of experience because docetaxel has been combined with a lot of drugs so far and all the trials are negative. So I don’t know whether or not we are going to have a positive trial in the future with docetaxel plus something so we are facing negative and negative trials. So I’m not sure that docetaxel should be given with another drug, we should maybe try to work on the selection of patients instead of adding drugs all together. I think we should work on personalising treatment and to find which drug corresponds to which patient. And we need to move to this way of thinking and strategy and you’re aware about that and you’re working on that. So really now we need to give the right drug to the right person at the right time and we need to work on the predictive factors, prognostic factors in order to avoid toxicity, cost of those drugs and so on.

So finally I’d just like to ask your thoughts about the role of chemotherapy in the years to come because we’ve got all these exciting new drugs, we’ve got abiraterone, we’ve got enzalutamide, radium-223 and I could imagine that they might all be used before chemotherapy and chemotherapy could get later and later. What do you think?

I think that, yes, I am sure that a monotherapy is going to move earlier in the stage of the disease but maybe for some patients, I am thinking about patients with neuroendocrine differentiation for instance, Gleason 8-10, liver metastasis, very short PSA doubling time, those patients who have the rarest disease, I’m not sure that hormonal therapy will have an effect on those patients. So maybe we need really to select according to this parameter, pain, no pain, short PSA doubling time, neuroendocrine differentiation, Gleason score and so on, to really see which drug could really help the patient. We don’t have to fight one laboratory to another but really to work altogether, that you propose to the patient the right drug.

So chemotherapy still has a future then?

I think so, yes.

Thank you very much Stéphan.

Thank you.