Dosing and Combinations of Sunitinib Vis-à-Vis Alternative Therapies for RCC
Dr. Haffizulla: Welcome to this PracticeUpdate. I’m Dr. Farzanna Haffizulla. Joining me today is Dr. Eric Jonasch, Professor in the Department of Genitourinary Medical Oncology in the Division of Cancer Medicine, and Director of the VHL Clinical Center at the University of Texas’s MD Anderson Cancer Center. Dr. Jonasch, wonderful to have you back.
Dr. Jonasch: Great to be here.
Dr. Haffizulla: So, Dr. Jonasch, there are multiple trials out now comparing sunitinib to novel combinations, including PD-1-based therapies, and most of these studies are truly tethered to the traditional sunitinib 4-2 schedule. Do these studies give sunitinib a fair shake given your data related to alternative dose scheduling?
Dr. Jonasch: Really good question and the answer is actually a little complicated. So, we’ve just completed our initial analysis of our 2-1 sunitinib study, which we just presented at GU ASCO, where we show that our primary endpoint of toxicity was actually not met. We did see that there was about 25% of patients who had grade 3 toxicities of diarrhea, hand-foot syndrome, or fatigue, but what we did observe was that the efficacy in this study was extremely high. We saw a long progression-free survival of 19 months. We see that our median survival has not been yet reached, and we have a response rate of 55% with one complete responder.
So, there’s something interesting going on here with regards to efficacy. So, if you now look at a phase 3 study where you’re comparing efficacy of sunitinib in the traditional schedule of 2 and another combination, maybe the sunitinib in the 4-2 schedule is being hampered by the virtue of the fact that people are going to come off sooner because of the toxicity. You can’t respond to a drug if you’re not receiving it. So, early days. Intriguing question. I think we need to do a little bit more digging both in our data and the data of other individuals who have explored alternate schedules, but I think we can probably increase the efficacy and the tolerability of sunitinib by alternating the schedule and the dose.
Dr. Haffizulla: Absolutely. Now, I wanted your comments on the results of the IMmotion150 trial. The trial that’s a randomized phase 2 trial looking at sunitinib versus atezolizumab versus bevacizumab plus atezolizumab. What do they imply for patients with this disease?
Dr. Jonasch: So, this study shows that the efficacy of the combination is not greatly superior to that of sunitinib monotherapy, and the number of partial responses and complete responses is not dramatically different. It’s a small study, and it’s actually being followed on currently by a randomized phase 3 study, IMmotion151, which probably is going to give us some more definitive data, but it does provide us a little bit of a cautionary tale with regards to these combinations. That potentially not all anti-VEGF agents are the same in how they modulate the immune microenvironment and the tumor microenvironment and that perhaps not all checkpoint antibodies are the same either.
So, right now, I would say that the only thing that we have is a question mark and a cautionary note, but we’re going to have to wait until we get phase 3 data to be able to see whether or not this less than stellar performance is actually going to be borne out by these phase 3 trials.
Dr. Haffizulla: Oh. So, time will tell.
Dr. Jonasch: Exactly.
Dr. Haffizulla: Well, I want to thank you for sharing your expertise and giving your comments and for all that you’re doing here at ASCO GU 2017.
Dr. Jonasch: Thank you.
Dr. Haffizulla: To our viewers, thank you for joining us for this PracticeUpdate. I’m Dr. Farzanna Haffizulla.
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