Practice Update | Onology

CONFERENCE COVERAGE 20

Novel treatment options for RCC: a review Interview with Bradley G Somer MD

Dr Jennifer Caudle speaks with Dr Somer, Assistant Professor in the Department of Hematology/Oncology at the University of Tennessee Health Science Center and Senior Partner at West Clinic in Memphis, on pembrolizumab plus IDO1 inhibition for advanced renal cell carcinoma, and the ProtecT trial involving VEGF-directed therapy.

Dr Caudle: You and your colleagues pre- sented data related to the combination of pembrolizumab and an IDO inhibitor in patients with advanced kidney cancer. Can you tell us about this dataset and its implication for this disease? In particular, is combination immunotherapy a viable strat- egy in renal cell carcinoma, and how might this combination compare to nivolumab/ ipilimumab? Dr Somer: A lot of questions there. I’m going to tackle them one by one. This dataset was an expansion cohort of the combination of pembrolizumab and a drug called epacadostat, an oral agent that is an IDO1 inhibitor. Now the big rage is trying to find combination immunother- apies… and this was an expansion cohort of renal cell carcinoma; clear cell carci- noma patients [and] most had received prior therapy. An IDO essentially is an immune regula- tory molecule, an enzyme that actually metabolizes tryptophan in the tumor microenvironment. When that happens, it essentially creates an immune suppres- sive effect on the local area. For example, the placenta makes a lot of IDO so that a mother’s immune system can’t detect the

The added bonus is that epacadostat doesn’t really add that much to toxicity to what you might see with a checkpoint inhib- itor alone. Maybe a little more rash, but it seems that the side effect profile was very similar to what you might expect with pem- brolizumab alone, so it looks promising. What I was going to say also, you men- tioned other combination immunotherapy like nivolumab with ipilimumab, there’s some early data showing good response with that too; enhanced response at like 40% or so. There’s added toxicity when you combine it with ipilimumab. The main thing [we’re] looking at now is what combina- tion therapy works the best with the least amount of side effects. I think the jury’s still out on that, but there’s clear proof of con- cept to push this to the next level. Dr Caudle: Data from the ProtecT clinical trial is being presented at this meeting. Can you tell us a little bit more about how this dataset will affect your clinical practice for patients with localized kidney cancer? Are there any patients for whom you might consider adjuvant VEGF-directed therapy? DrSomer: This is a very interesting story in the sense that we know adjuvant therapy, in a lot of solid tumors there’s clear benefit. But dexamethasone are very, very active and I think that’s probably the most pressing question, at what point should that become the standard front-line therapy and the sec- ond question of course is the daratumumab question. Everyone is very interested. Dr Jakubowiak presented a study in that regard and an impressive result, but the reason I say it’s harder because there are so many options and we just want to get really smart about how we go about com- bining these agents. During the session, I was thinking about this and they were presenting so many clinical trial results. The one thing that struck me the most is the importance of achieving MRD, which really is becoming the central point for the development of new combinations. And

placenta. Tumor utilizes that mechanism to make itself invisible to the immune system. By using this drug (epacadostat) to block IDO, it can regulate the immune system to enable it to work more effectively. When it gets combined with pembrolizumab, which also is an immune checkpoint inhibitor, that’s a combined immune effect. Basically the point of this study was to look for what might be considered an enhanced activ- ity, and then looking at the potential safety effects of it. Their efficacy was looked at in 30 patients with clear cell carcinoma of the kidney. A third of the patients had a response and about 50% or so had a clin- ical benefit. What was interesting was that if you looked at the patients who had zero to one prior line of therapy, it was about 47% response and close to 60% clinical benefit. If you look at just the checkpoint inhibitor alone, like nivolumab for example, probably about 15% to 25% response. So looking at some- thing that might provide 33% response or 50% response, that’s kind of pushing it beyond where you might get with just a sin- gle-agent checkpoint inhibitor. So it lends at least the possibility that this combination effect is real, and hopefully to go into the next phase of development.

Practice changers inmyeloma Interview with Rafael D. Fonseca MD

Dr Farzanna Haffizulla speaks with Dr Fonseca, Chair of the Department of Internal Medicine at the Mayo Clinic, on novel combinations for the treatment of myeloma and whether these could form the new standard of care for front-line therapy.

Dr Haffizulla: A number of studies this year report the use of novel combinations up front for the treatment of myeloma. How close are we to a new standard of care for front-line therapy? Dr Fonseca: That’s a great way to phrase that question. It goes without saying that we’re getting better and better at achiev- ing very deep responses, very durable responses as well too in the front-line setting. And the questions right now are

what are the best agents, how should they be combined, and of course, the second part of the question is should we be add- ing monoclonal antibodies? Actually, this morning we saw two presentations, one where they added elotuzumab, one where daratumumab was added, and it’s a little bit early to say whether any of those actu- ally changed the standard of care at this point. But we’ve learned that the combina- tions of carfilzomib with lenalidomide and

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