The abstract is relative to another phase II study which another academic phase II study led in Milan as a single site trial with the use of alisertib in refractory and chemotherapy pre-treated urothelial carcinoma. Alisertib is a spindle checkpoint inhibitor so basically it has been developed in lymphomas, in hematologic disease, and also in ovarian cancer with promising signals or signals of activity. The target is the aurora kinase A which is still poorly understood in terms of clinical impact in urothelial carcinoma despite a good rationale. So we developed a phase II study with this drug as a single agent for patients who have failed at least one chemotherapy regimen.
Unfortunately the first stage of this trial the required number of responses was not met so the study was concluded after the first twenty patients. Despite these low signals of clinical response we observed very, very interesting signals of a possible advantage in overall survival. The median overall survival was not reached after a median follow-up of 8.3 months meaning that probably there would be a signal towards an improvement in overall survival for these patients, this is interesting. But the major problem is trying to identify the patients who should be selected for this kind of treatment which is very, very difficult. We started doing that, sequencing the outlier patients, and some signals of gene mutation that may be linked to clinical activity of this drug are being collected but are at a very, very early stage so too early to state anything so far.
So it’s too early probably to conclude that this kind of drug, this family of drugs, is effective in this disease but, of course, tolerability was a concern and it was a concern based on the development of immunotherapy on the other side in this disease which is completely changing the scenario of treatment in this disease. So developing anything else outside immunotherapy is becoming more and more difficult in this disease. But interesting signals of long-term survival are being collected with this drug.
What’s the next step for this data?
It’s very difficult to identify the next step. Probably the next step may be identified only if we clearly identify an association between a molecular profile or something like that and the response to this family of drugs or this kind of drug. Otherwise immunotherapy so far is a privileged pathway towards the registration as a standard of care of many drugs. So it will be difficult to envision a future for this kind of drug, like spindle checkpoint inhibitors, in this disease.
Are there other treatment options in this setting?
Basically we have no option, no conventional option. The only drug which is registered in urothelial cancer after failure of chemotherapy is vinflunine but only in Europe, not the United States. So it’s clearly an unmet medical need, clearly up to one year ago there was nothing circulating in clinical trials and now there are many new drugs, many immunotherapy drugs, many immune checkpoint inhibitors that are completely changing the scenario of the salvage setting. So we still don’t have any registered drugs which is a standard of care but we will have so in a very few years with something that will change the future of these patients.