In this meeting I'm presenting a collaborative study done through eight centres in the UK looking at the use of vinflunine chemotherapy in penis cancer. The background is that there are actually very few prospective studies in penis cancer that have ever been done at all and even fewer in advanced disease. The studies that we do have, which partly to date have been retrospective, largely small studies, have shown that combination chemotherapy can be effective but the response rates are not particularly high and also the toxicity is appreciable. So therefore what we wanted to examine was whether you could give a single agent chemotherapy, so vinflunine, to a group of patients with locally advanced and metastatic penis cancer and to see whether you could deliver that successfully with appropriate levels of toxicity and with meaningful clinical benefit.
We conducted an open label phase II study where we needed to recruit a minimum of 22 patients who would be evaluable for the primary endpoint which was objective response plus stable disease, giving overall clinical benefit rate. Any patients who dropped out of the study before the primary endpoint were replaced so actually we recruited a total of 25 patients. All the patients received vinflunine chemotherapy who were eligible to do so and this study gave four cycles of chemotherapy to be evaluable for the primary endpoint. In fact, patients who were tolerating the chemotherapy well were able to continue chemotherapy beyond four cycles if they were deriving benefit in the opinion of their local investigator.
What do you find?
The study met its primary endpoint. By the statistical design we needed to see a minimum of seven cases where there was stable disease or objective response, in fact we saw ten. That gave an overall clinical benefit rate of 45.4% which exceeded the threshold for the primary endpoint which, in fact, was 40%. We also saw that there were six patients who had an objective response with an additional four who had stable disease. The progression free survival is 2.8 months and median overall survival was 8.5 months. That's quite small but actually is in keeping with what we'd usually find.
There was toxicity from the chemotherapy, this is a cytotoxic chemotherapy. So there were a number of patients with neutropenia, anaemia and some with sepsis as well. Overall, therefore, we found the chemotherapy was deliverable to this patient group. One of the criteria for the study was that if patients had locally advanced disease their treating clinical team had to deem them unsuitable for combination chemotherapy. So, therefore, the fact that we were able to deliver chemotherapy successfully to this group, some of whom had already been deemed to be unsuitable for combination chemotherapy, is a success. Therefore what we found in the meaning of this is that we have another chemotherapy that has been proven to be effective in the treatment of advanced penis cancer and is suitable for patients who are not suitable themselves for cisplatin chemotherapy and that's the first time that that's been shown.
One might say that the standard in this setting to date has been cisplatin-based combination chemotherapy. As I've said, that can be quite difficult to deliver to some patients due to its toxicity and so we were looking for a different option for the patients deemed unsuitable for cisplatin. Because of the rarity of penis cancer it's quite hard to conduct randomised studies. There has never been a randomised study to date in penis cancer globally anywhere. There have, in fact, only ever been three or four positive prospective studies at all, all of which were phase II. So this is a very new and emerging field and actually shows what can be done with collaboration within the UK. To do a randomised study would absolutely require global and international collaboration.