ESMO Preview: Treatment of Genitourinary Cancers Rapidly Evolving

Thomas Powles, MBBS, MD, MRCP

As part of our coverage of the European Society for Medical Oncology (ESMO) 2014 Congress, taking place in Madrid September 26-30, we are speaking with Prof. Thomas Powles, MBBS, MD, MRCP, clinical professor of genitourinary oncology at Barts Cancer Institute and an invited discussant at a poster discussion session on non-prostate genitourinary tumors. 

  -Interviewed by Leah Lawrence 

Cancer Network: Dr. Powles, can you tell us what in your mind sets ESMO apart from some of the other major medical meetings, and what are you looking forward to this year at the meeting? 

Dr. Powles: ESMO is Europe’s biggest oncology meeting, and the oncology field is moving very quickly at the moment, particularly in the cancers that I am involved with. It is an important meeting. The thing that sets it apart, with the exception of ASCO, which is also a global oncology meeting, is the fact that it is so large and so much new data is presented. Historically, at other meetings, it is often the case that data is rehashed or re-presented, but this is where new data is presented, and for that reason it is really worth going to.  

Cancer Network: You are serving as a moderator for a poster discussion session on non-prostate genitourinary tumors, can you briefly discuss the three posters included in the session and what makes them interesting?

Dr. Powles: The first poster (812PD) is by Maria De Santis. She has done a randomized trial with a number of colleagues looking at vinflunine with either carboplatin or gemcitabine in the first-line setting of metastatic bladder cancer. Vinflunine is a drug which may or may not have a lot of activity in this setting. We don’t really know. There is a randomized trial being done against placebo in the second-line setting, and it doesn’t look spectacularly active-it doesn’t look a lot better than placebo. Combining it in the first-line setting-there is strong rationale for doing that because we have done lots of combination chemotherapy studies in bladder cancer before. But when you look back on it, overall, it doesn’t look like either of the two regimens sets themselves apart from regimens that are available to us at the moment. It looks like vinflunine, in combination with carboplatin or gemcitabine, is active, but it also has significant toxicity, of course.

What this is beginning to tell us is that it doesn’t really matter what combinations you use in patients who can’t have cisplatin-these are non-cisplatin eligible patients-in this group it looks like any doublet is active. I use gemcitabine and carboplatin, and it is an entirely reasonable thing to do. I don’t think we need to do lots more trials in this area. We know that progression-free survival is modest, it is a few months, and overall survival is also modest tending to be around the 1-year time mark. Overall, when you look at this group of patients, we need to find newer therapies.

That brings us to the second paper, Andrea Apolo’s work (811PD) looking at cabozantinib, which is a drug that was recently tested in prostate cancer and has a license in thyroid cancer. It is an oral drug that targets VEGF in the same way that sunitinib does, but targets MET as well. It is a combination of these two together that looks promising in this tumor type. Some of the work that Andrea is presenting is looking to see if there are biomarkers associated with response or resistance. Does MET overexpression in the tumor type correlate with outcome, response, or toxicity? One of the things shown in this paper is that it is actually quite difficult to predict who is going to do well and who is going to do badly with this drug. Indeed, there are not randomized trials with this drug at the moment in bladder cancer, so this is very preliminary. Effectively what it is telling us at this stage is that we haven’t yet found a biomarker. It is a promising drug, and if we are going to do randomized trials with it we can’t currently be selecting patients. I think that is relevant because we are going to do some randomized trials of it [in the future]. There is going to be a UK study, a national study, looking at randomizing cabozantinib after chemotherapy. This work has helped us design that trial.

The third paper is work from the global G3 germ cell tumor group (813PD). Lots of investigators around the world looked at treatment and outcome of patients with testis cancer who develop brain metastases. What the results of this study show, and this is quite important because we know nothing about this area, is that those patients who present with brain metastases do not have a great outcome. The majority of patients die of their disease, but if you relapse in the brain the outcome is even worse. We sort of knew that, or thought we knew that, but this is the first work to really demonstrate it. It also identifies a prognostic index in both groups of patients, which will better allow us to give patients information about what is likely to happen in the future. We can tell patients with brain metastases who are going to do well and patients who will do badly. The final part of this is it also tells us a little bit about treatment, and lets us know that not only is chemotherapy important in primary disease but in relapsed disease. It looks like multimodality therapy in terms of surgery and radiation on top of chemotherapy probably has a better outcome than chemotherapy alone. There was some selection bias involved in that, but this data will allow us to write new guidelines for patients with metastatic germ cell tumors in the brain.

Cancer Network: Outside of this session, what is some of the other research coming out of the meeting that you are looking forward to hearing?

Dr. Powles: We are all excited about immune-oncology at the moment. There is some interesting work looking at the combination of bevacizumab and PD-L1. There is also some data looking at the Merck PD-1 inhibitor in bladder cancer. I am very interested in these two studies. There are also a couple of randomized trials in renal cancer that I think are exciting. One trial is looking at the addition of an endothelin antagonist to mTOR inhibition, and the second trial is looking at inhibition of SRC in addition to VEGF inhibition in renal cancer. So there are a couple of randomized trials in renal cancer-that I think are probably going to be negative-but what that will tell us is that we have reached the ceiling of what we can do with targeted therapy, and we will look to immune-oncology studies to see if we can make major breakthroughs in two big cancer types.

Cancer Network: Thank you for taking a few minutes to speak with us today.