ASCO 2010 Annual Meeting, 4—8 June 2010, Chicago

Interview with Professor Ignace Vergote (Catholic University of Leuven, Belgium)

NKTR-102: a new drug for treating platinum-resistant or refractory ovarian cancer

What did you present at ASCO 2010?

I will be presenting the first results on the new drug.  It’s called NKTR 102, which we have tested in a difficult group of ovarian cancer patients, whose disease is resistant to platinum drugs.

How large was the study and what have been the key outcomes?

The total is 71 patients; the study was a randomisation between two regimens with the new drug, every two weeks or every three weeks, and what is important to notice is that these patients were heavily pre-treated, a median of three chemotherapy regimes, and that 58% of the patients had progression during platinum or recurrence within three months.  This means that this is a very bad group; in addition, 50% had resistance to the anthracycline, the pegylated liposomal doxorubicin (Caeylx in Europe, Doxil in the US), so we were surprised to see that the response rate,  which is the primary endpoint, was quite good.  The confirmed response rate in the three weekly regimen, which is the one we have chosen for the future, was 23% and based on the GOG definition, as we call it, which is based on RECIST and Ca125, response rate, was 38%, which is certainly interesting.  So the platinum-free interval was much shorter than the progression-free survival on the drug, meaning that this drug really adds something, in our opinion.

Perhaps I can tell you also something about the side effects.  The side-effects are quite limited.  The drug has very little neutropenia or thrombocytopenia, no hair loss, no neuropathy.  The only important side-effect is diarrhoea and this is logical because, as a matter of fact, NKTR 102 is a type of irinotecan but pegylated.  And due to the pegylation, the side-effects are less, and the drug stays much longer, more than three weeks, in the body, resulting in , good responses and fewer side-effects.

What message should clinical oncologists take from the results of this study?

There is a new drug on its way in the very difficult group of platinum resistant patients.  Obviously, the next step will be to do a large randomised trial comparing it with the current standard in this group of patients, which is normally pegylated liposomal doxorubicin, while at the same time drugs which result in such response rates, which are higher than paclitaxel or docetaxel, or all the other drugs which we have tested.  We would certainly be interested to see if this can be combined with carboplatinum and used in both platinum sensitive disease or in the first line.  But that’s for the future.

What is the key message patients should take from this study?

Patients are interested in it, especially when they hear that there is no treatment available anymore, because often when they have had three or four lines of chemotherapy, they are platinum refractory,.  So I think patients are interested now already, at least where I live, in this drug, because it’s a drug with relatively few side-effects though better response rates and progression free survival is probably too early to say