Brian Rini, MD, FASCO

GU Oncology Now

A roundtable discussion, moderated by Brian Rini, MD, of the Vanderbilt University Medical Center, focused on the spectrum of therapy for frontline renal cell carcinoma (RCC), including a comparison of monotherapy and doublet and triplet treatment options. Dr. Rini was joined by a panel that included Monty Pal, MD; Moshe Ornstein, MD; and Shuchi Gulati, MD, MSc.In the final segment of the roundtable series, the panel shares interesting clinical trial data in development, including CONTACT-03, TiNivo-2, and more.&mdash;Dr. Rini: Let&rsquo;s close with new data you&rsquo;re looking forward to in the next year. Or drugs, we didn&rsquo;t touch on belzutifan, a HIF inhibitor. What&rsquo;s exciting? What do you think is going to come out and impact practice? <a href="https://guoncologynow.com/post/checkmate-8y8-trial-in-progress-what-are-the-implications-for-this-doublet">We talked about CheckMate 8Y8</a>, so we&rsquo;ll take that off the table. What other data is coming, and what might be most impactful?Dr. Pal: I don&rsquo;t know how soon it&rsquo;s coming, but this phase 3 trial of everolimus versus belzutifan in heavily refractory patients probably is going to be the first I would imagine of these phase 3 studies to hit. I can&rsquo;t imagine that belzutifan wouldn&rsquo;t win out against everolimus with the response rate of 2% and a progression-free survival (PFS) of 1.6 months in its own phase 3 trial. If belzutifan doesn&rsquo;t hit the bar, we have a problem. Once that agent comes into practice, I think the big dilemma is going to be do we go tyrosine kinase inhibitor (TKI)/immuno-oncology (IO) to TKI and then to an agent like tivozanib? Or will we go down the path of belzutifan? It&rsquo;s going to be a really interesting dilemma. I&rsquo;m not quite sure what I&rsquo;ll do at this point.[Editor&rsquo;s note: This discussion was filmed prior to the release of results from the CONTACT-03 trial. <a href="https://guoncologynow.com/post/contact-03-primary-pfs-analysis-of-atezolizumab-plus-cabozantinib-after-progression-in-mrcc">Read more updated information</a> on the trial&rsquo;s findings.]Dr. Rini: I&rsquo;m not either. Shuchi, what are you looking forward to?Dr. Gulati: Definitely the belzutifan and also the CONTACT-03 data to guide us on the sequencing question.Dr. Rini: CONTACT-03 is cabozantinib/atezolizumab versus cabozantinib in an IO-refractory population. TiNivo-2, which is still accruing, is tivozanib/nivolumab versus tivozanib in pretty much that same population, including post-adjuvant, so adjuvant pembrolizumab failures were allowed in CONTACT-03 as well. We&rsquo;re not going to cover that, but that&rsquo;s a whole segment of patients we have no idea what to do with. It&rsquo;s kind of asking, do patients get a second shot at immune therapy? Do you think for those studies there has to be an overall survival (OS) benefit for the them to get used? I think they&rsquo;re probably PFS/OS co-primaries.Dr. Pal: It&rsquo;s going to be so hard to demonstrate an OS advantage, and that hasn&rsquo;t really been our bar in the refractory setting to date.Dr. Rini: Maybe it should be.Dr. Pal: Maybe it should be.Dr. Ornstein: Up until now, the bar for frontline has been OS, and the bar in the refractory setting has really been the PFS benefit.Dr. Rini: But I guess I would counter, and I&rsquo;m not sure I have a strong opinion on this, that&rsquo;s because we haven&rsquo;t had curative drugs in the refractory setting. We would hope that immune therapy can be curative in the refractory setting. If there&rsquo;s a statistically significant PFS, they&rsquo;ll get approved and used. We say, you can&rsquo;t show OS when we haven&rsquo;t shown it. Then a potent drug comes along and suddenly you show it. That has happened in other diseases. Do you think there will be an OS advantage?Dr. Ornstein: I don&rsquo;t think so. I&rsquo;m not convinced there&rsquo;s going to be a PFS advantage. We don&rsquo;t see a ton of PFS benefits from IOs in general, and I think something happens to a patient&rsquo;s RCC biology when there&rsquo;s disease progression on an IO agent, and I&rsquo;m really not convinced about the activity. We had TiNivo-2 and CONTACT-03 open and we accrued. I think it&rsquo;s an important question to answer, but I&rsquo;m really curious to see the results.Dr. Pal: I&rsquo;ve just seen so many patients referred into my practice who have been on 3 or 4 sequential IO-based therapies. I&rsquo;m just thinking to myself, what an amazing societal economic cost. This is coming out with zero data.Dr. Rini: There&rsquo;s an immunotherapy halo effect, right? Where you might not do that with a MEK inhibitor or something else. There&rsquo;s this halo effect because you&rsquo;re always holding out for that durable disease control. We&rsquo;ve all had patients who were rescued. We all have those dramatic patients who were rescued. It&rsquo;s a bit in desperation. I&rsquo;m not justifying it, but I think I understand the philosophy.Dr. Pal: I was doing this talk last night with Dave McDermott, MD, and Chuck Drake, MD, was actually in the audience, which was amazing. It was a great opportunity. I don&rsquo;t know why he came to my talk. I asked him, &ldquo;What do you think about this principle of IO followed by IO?&rdquo; He said, &ldquo;To many folks out there treating breast cancer and other diseases, the paradigm exists.&rdquo; With HER2-directed therapies, for instance, you use that through the continuum of treatments for breast cancer. ER/PR-positive is the same. There is that paradigm in oncology, but we probably do need to try to deflate it if it&rsquo;s not helping patients.Dr. Rini: There&rsquo;s the paradigm, but diseases are different. Like you said, myeloma is different. We certainly need level 1 evidence.&mdash;<a href="https://guoncologynow.com/page/renal-cell-carcinoma-roundtables">Watch more RCC roundtable videos.</a>

Panelists Weigh In on Interesting Data Still to Come in RCC

Roundtable

The panel shares interesting clinical trial data in development, including CONTACT-03, TiNivo-2, and more.