Bladder Cancer Update & Renal Cell Cancer Update, 2017 (Video Program)VEGF tyrosine kinase inhibitor (TKI)-based therapy for patients with bladder cancer
4:32 minutes.
TRANSCRIPTION:
DR GALSKY: Targeting VEGF receptor and other kinases with multitargeted tyrosine kinase inhibitors that inhibit VEGFR and other kinases as well has been explored in bladder cancer over the past decade. So there have been trials with sunitinib and trials with pazopanib. And both of those trials have shown objective responses in a very small percentage of patients but do establish some proof of concept that it’s probably possible to elicit a response to single-agent therapy with these drugs. And so that has led to some interest in testing some of these newer-generation multitargeted kinase inhibitors, including cabozantinib. So there’s a trial of cabozantinib as a single agent at the National Cancer Institute, which has been presented in preliminary form and shows an objective response rate in about the 20% to 30% range with these therapies. That has led to a couple of approaches, but probably one of the most interesting approaches, based on some evidence showing immune modulation with cabozantinib in urothelial cancer patients, has been to combine cabozantinib with nivolumab or with nivolumab and ipilimumab. And that’s a study that’s ongoing. That’s being led by the NCI. DR LOVE: Yes. I kind of knew what the next part of that sentence was, because I’ve heard that with other tumors. And I’ve heard even bevacizumab as potentially having an immunologic basis. And, for that matter, has bevacizumab been looked at in bladder cancer? And any thoughts about why there might be synergy between VEGF and checkpoint inhibitors? DR GALSKY: So the bevacizumab story so far is based on some suggestion that T cells can infiltrate the tumor better with VEGF inhibition. And that’s been pretty nicely shown in kidney cancer with post-treatment biopsies in patients receiving combination VEGF inhibition plus PD-L1 inhibition, showing a higher frequency of T-cell infiltration than compared to single-agent PD-L1 inhibition. Now, those are very small numbers but really do establish some proof of concept based on what was anticipated to happen based on data in model systems. That hasn’t been studied yet in bladder cancer. However, there is an upcoming study that will be managed through the Hoosier Cancer Research Network in cisplatin-ineligible patients randomizing patients to atezolizumab alone versus atezolizumab plus bevacizumab. DR LOVE: In terms of TKIs, have you yourself administered any of these VEGF TKIs to patients with bladder cancer on a trial? DR GALSKY: So sunitinib on trial and pazopanib on a few patients off trial before we had some of these newer treatments available. DR LOVE: Any objective responses or useful responses? DR GALSKY: I haven’t seen objective responses myself. I have seen some patients with stable disease for whom it’s of course difficult to know how much impact the treatment had. What I should point out is that there are some data from Monty Pal at City of Hope showing the use of pazopanib in patients with FGFR3-mutant bladder cancer, given that one of the kinases that pazopanib targets, although not at very high potency, is FGFR. DR LOVE: Are there situations where you would consider giving one of these TKIs? You mentioned some pretty encouraging data with cabozantinib, for example, outside a trial setting. DR GALSKY: Yes. So of course, with more and more treatments available in this disease and more and more trials available, that’s really become a less common scenario where I’m facing that decision. And in the past, the number of trials available for patients with metastatic urothelial cancer has been incredibly small. And we were really looking for anything that might have an inkling of benefit for our patients. And now there’s just a huge number of clinical trials and, in fact, probably as many clinical trial slots as there are patients. So of course that’s always the first consideration. But, given that these drugs are available and there is some compelling data for the right patient, it could be a consideration. |