The expert panel discusses trials underway in the adjuvant setting and the role of adjuvant therapy in patients with RCC.
Robert Motzer, MD: Let’s move on to a couple of other general questions and get takes from the other panel members in terms of these data.
A question for Tom in terms of you were involved in the adjuvant TKI [tyrosine kinase inhibitor] trials. What is your take on the tolerability of PEMBRO [pembrolizumab] in this study compared to what we’ve seen with the VEGF [vascular endothelial growth factor]/TKIs in the adjuvant trial? Do you think the safety profile was reasonable? Are you concerned about the adverse events that were observed in this trial for these patients?
Tom Hutson, DO, PharmD: No, I think it’s much more favorable and much more tolerable, much more livable, and will allow patients who are potentially already cured to try to continue with a better lifestyle. We really saw significant adverse effects, much greater in that patient population than we saw in the metastatic setting using TKIs. This is definitely a step in the right direction with all the characteristics of something that would be very livable for a patient, that a patient would want to do, again remembering that they may already be cured. Thus, having the least impact on their normal daily living.
Robert Motzer, MD: One of the big questions is, assuming [pembrolizumab] is approved in the adjuvant setting, for patients who are treated with [pembrolizumab] in the adjuvant setting and then they relapse, again, this will be a big change to our paradigm. How do you see this influencing first-line therapy, Eric, in terms of patients who are treated with [pembrolizumab] and then relapse with metastatic disease?
Eric Jonasch, MD: Thanks for giving me the easy questions, Bob. This is a data-free zone. I would imagine that if you had an individual who is relapsing multiple years down the line, that you would probably consider them treatment naïve to some degree. But more importantly, an individual who is on adjuvant immunotherapy and then progresses while on therapy, what do you do? I would say that I would add a TKI on to the I-O [immuno-oncology] therapy in this situation and hope that that’s going to really provide a benefit for that person. If they’re on adjuvant pembrolizumab, I would add lenvatinib. We have no information on what to do for these individuals, but that would be my logical first choice.
Robert Motzer, MD: That is an interesting discussion without data. Let’s just take a quick poll of the panel members. Tom, for your patient who receives [pembrolizumab] adjuvant and then relapses say a year later, what is your go-to treatment, or the same patient who relapses 6 months into [pembrolizumab]?
Tom Hutson, DO, PharmD: Yes, that’s tough. We don’t know yet whether there’s a time impact like there is with cytotoxics with defining what absolute resistance means and refractoriness. But I think it’s reasonable to do what Eric mentioned, which is to do [lenvatinib/pembrolizumab] or even consider changing the regimen, the PD-1 or PD-L1.
Robert Motzer, MD: These are all questions in a rapidly changing paradigm of RCC [renal cell carcinoma], based on advances that we’re making. But I think that the adjuvant setting has been an area of high unmet need. Also, this is one of several studies, the first one to read out, but let’s just take a look at the others for a minute so people can be aware. There’s been a number of large randomized phase 3 trials that are all addressing either adjuvant or neoadjuvant therapy, and these are shown in this slide here. The IMmotion010 trial is a large randomized adjuvant study of atezolizumab versus placebo, and that trial completed accrual, and hopefully will have a readout soon with that.
The CheckMate 914 is the only study that is still open for accrual in the United States as well as globally. This was a trial that initially started out as a randomized comparison of NIVO [nivolumab] plus IPI [ipilimumab] to placebo and completed enrollment of about 800 patients, and then set out with a second schema of [nivolumab] plus [ipilimumab] versus [nivolumab] versus placebo in a 1:2:1 ratio to address the role of monotherapy with nivolumab as well. This trial is well into accrual but is one that is enrolling in the United States.
The PROSPER study is a trial that has been run through the Eastern Cooperative Oncology Group that is interesting in that it addresses both neoadjuvant and adjuvant questions, and that has completed enrollment as well. The fourth trial is the large RAMPART trial, which is being run in the United Kingdom mostly and some other countries in Europe. That is looking at additional checkpoint inhibitors compared to surveillance, an AstraZeneca-sponsored study. I think these are all 4 big studies that will provide additional insight and information of value in this new era of adjuvant I-O therapy for RCC.
Hence, I’d to thank our excellent panel for your thoughtful case discussions and the wonderful discussion you all provided. To our viewing audience, thank you for joining us for this Targeted Oncology™ Virtual Tumor Board® presentation. We hope today’s discussion was a valuable use of your time, and that you acquired some practical knowledge that you can take back to your clinic. Thanks very much for attending.
Transcript edited for clarity.