Rechallenging Treatment in Third-line and Subsequent RCC Settings

A roundtable discussion, moderated by Monty Pal, MD, of the City of Hope, focused on updates in renal cell carcinoma (RCC), including treatment in both the frontline and adjuvant settings. Dr. Pal was joined by a panel that included Daniel George, MD; Brad McGregor, MD; and Cristina Suárez Rodríguez, MD.

In the next segment of the roundtable series, the panel debates the “phenomenon” of rechallenging treatment in subsequent treatment lines and what clinical trial data indicate on the topic.

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Dr. Pal: Let’s say we’ve committed to starting our patient frontline on tyrosine kinase inhibitor (TKI)/immuno-oncology (IO). The practice that I’m seeing a lot is the patient might go through 1 or 2 additional lines of therapy, perhaps with a TKI, perhaps with TKI plus IO again, and then receive nivolumab/ipilimumab on rechallenge. What do you think about that? This phenomenon of rechallenging with nivolumab/ipilimumab in the third-, fourth-, fifth-line setting?

Dr. Suarez: If I could do it?

Dr. Pal: If you could do it.

Dr. Suarez: We have the data for nivolumab/ipilimumab, and the data is not very, very exciting. Our response rate I think is around 15% or something like that, with no patients showing complete responses. I don’t know about that. I think that for me, a key question is what you mentioned, it’s the ongoing trials; we have the CONTACT-03 trial and TiNivo trial using immunotherapy after immunotherapy without stopping. This will not answer the question of rechallenging with immunotherapy. We know from many other treatments that it’s good if you stop using the same target and then you use it again. I think that that trials will answer it. If they’re positive, that’s nice. We need to maintain the immunotherapy. But if they are negative, as you mentioned, I think it doesn’t mean that you cannot retreat the patients with immunotherapy in the future in third or fourth lines.

Dr. McGregor: To that point, the trial designs are different. In CONTACT-03, you have to have IO as the most recent line of therapy, and you go on to cabozantinib with or without atezolizumab. But TiNivo-2 actually you said had to proceed immunotherapy in the past, but you do not need immunotherapy as the most recent line. If you had immunotherapy and IO/IO, you could go to TKI and then still enroll in TiNivo-2. It’s a little bit different. To Dan’s point, there’s almost 2 different populations in TiNivo-2. We’re going to have that continued IO approach or there’s going to be those patients that had a break in therapy.

Dr. Suarez: I think they did an amendment now, and you need to come from the immunotherapy or something like that. You’re only allowed now 2…

Dr. McGregor: …prior lines of therapy.

Dr. Suarez: There are some other trials like the Umbrella 03B trial that is not going to give any answer because it’s multi-arm and it’s not a phase 3 trial but will give you some clues. In this trial are using lenvatinib/pembrolizumab but also different targets like belzutifan, you don’t need to come from directly from the immunotherapy. I think that it will not give any answers but some clues.

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Continue on to watch the next roundtable segment.