Current Research Gives a Glimpse Into the Future of GU Cancer Treatment

Multiple abstracts presented during the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) showed how the treatment landscape for diseases like renal cell carcinoma (RCC) and prostate cancer are evolving.

Specifically, treatment with adjuvant pembrolizumab (Keytruda) in patients with RCC who were at high risk of recurrence showed continued disease-free survival (DFS) benefit versus placebo (HR, 0.63, 95% CI, 0.50-0.80; nominal P < .0001) in the phase 3 KEYNOTE-564 clinical trial (NCT03142334).

There were 3 subgroups totaling 347 patients. All subgroups favored adjuvant pembrolizumab over placebo. In the intermediate-risk population, the difference between adjuvant pembrolizumab and placebo showed a hazard ratio of 0.68 (95% CI, 0.52-0.89), 0.60 in the high-risk population (95% CI, 0.33-1.10), and 0.28 in the patients with M1 no evidence of disease (95% CI, 0.12-0.66). The study findings signal a new standard of care for this patient population.

In prostate cancer and other GU malignancies, research on the use of PARP inhibitors and combination immunotherapies were impressive, according to experts like Sumanta “Monty” K. Pal, MD, FASCO.

In an interview with Targeted Oncology™, Pal, professor, Department of Medical Oncology & Therapeutics Research and co-director, Kidney Cancer Program at the City of Hope Comprehensive Cancer Center, discussed the most interesting research presented during ASCO GU.

TARGETED ONCOLOGY: What were the most practice-changing data reported for RCC during ASCO GU?

Pal: In my mind, the most interesting data that came out for renal cell carcinoma had to do with updates on adjuvant treatment. This basically just bolstered data that we heard last year from the KEYNOTE 564 trial that looked at pembrolizumab versus placebo in the adjuvant setting. The study really identified a persistent, durable benefit from pembrolizumab in terms of disease-free survival. I think it's encouraging for patients and for practitioners to see that the overall survival seems to be trending in the right direction as well. I think that's certainly a good omen for both patients [and providers]. It's also a good omen for the trials that are impending. I'm running a clinical trial looking at adjuvant atezolizumab [Tecentriq] and I'm hoping that that trial has a very similar fate.

What were the most practice-changing data reported in the prostate cancer space?

In prostate cancer, I think the big news was the development of PARP inhibitors in earlier settings. There are major trials looking at the addition of PARP inhibitors to agents like abiraterone. And the data really suggested a compelling outcome in some cases, so it's those patients that had DNA damage repair mutations and those that didn't. So, that was a little bit of a surprising result to me, and I'm looking forward to seeing some biological distinctions regarding why, for instance, in 1 trial looking at olaparib [Lynparza], we had a certain outcome versus a distinct outcome of the trial of niraparib [Zejula].

Were there any trials in progress that you think are notable?

I'll take a moment to highlight the trials in progress that have been hosted by City of Hope and this is actually a study that we presented at ASCO GU looking at cabozantinib [Cabometyx] and nivolumab [Opdivo] with or without the agent CBM588. CBM588 is a live bacterial product that increases the production of butyrate-generating species within the gut. We think that that might really enhance the host’s immune anti-cancer response. And so, what we've seen is that the combination of nivolumab and ipilimumab [Yervoy] has been enhanced. We're hoping to do the same with cabozantinib and nivolumab.

Fellows from City of Hope presented compelling work that builds on our experience with CBM588 with nivolumab and ipilimumab, and, specifically, they’ve actually been able to dissect the outcomes of different metabolic profiles of bacteria as it pertains to the study showing that certain classes of metabolism either enhanced or underrepresented amongst responders.

In prostate cancer, City of Hope presented some nice work looking at the correlation between mutations in the androgen receptor and outcomes in patients with prostate cancer through something called a PROMISE registry, a very large collaborative across multiple institutions. Finally, we also had data pertaining to COVID-19 antibody titers and GU cancer patients presented by 1 of my fellows and that data I thought was quite compelling and alluded to the possibility of antibody titers for the most part remaining relatively steady amongst those individuals who have received vaccination for COVID-19 with kidney, bladder, and prostate cancer.

Going forward, what are some clinical questions that you hope will be answered in GU clinical trials?

I think the most pressing question to answer in the context of clinical trials is whether or not we can potentially do things to add to the efficacy of drugs like immunotherapy, which ostensibly have led to durable responses, more so than any other class of drugs before, but also mitigate the toxicity. I think now we're talking about going to triplet, quadruplet, and quintuplet regimens. And at some point, we're going to have to start wondering about whether or not patients can actually tolerate this panoply of agents.

So, I think it's going to be critical for us to take a strong look at the regimens that we're using and determine whether we're going to be able to implement those in the clinic. And 1 strategy moving forward is to focus on the microbiome, using agents like live bacterial products. We've explored a drug called CBM588 to see whether or not you can use these very subtle additives to the patient's daily lifestyle, and greatly enhance outcomes.