Toni Choueiri, MD, on How New Data Impact the Standard of Care for RCC

An expert discusses how new data from the phase 3 CheckMate 9ER trial impact therapy choice in previously untreated advanced renal cell carcinoma.

Nivolumab (Opdivo) plus cabozantinib (Cabometyx) demonstrated improved efficacy and prolonged survival compared with sunitinib (Sutent) among patients with previously untreated advanced renal cell carcinoma (RCC), regardless of sarcomatoid status, according to results from the phase 3 CheckMate 9ER trial (NCT03141177) presented at the American Society of Clinical Oncology (ASCO) 2021 Genitourinary Cancer Symposium.

In an interview with CancerNetwork®, Toni Choueiri, MD, director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute/Brigham and Women’s Hospital as well as the Jerome and Nancy Kohlberg Chair and professor of Medicine at Harvard Medical School, discussed how these results may inform the standard-of-care in frontline RCC.

[CheckMate 9ER] is a study that led to the approval of that regimen in the frontline by the FDA in January…the patients now have another option. Yes, for physicians and healthcare workers and providers, the challenge may be tougher to pick an ideal situation. But I think people…who are versed enough in knowing some of the nuances [know] what to pick over what.

I recently launched a poll on Twitter, and it provided information. It was [about] a 68-year-old patient [who presented] with metastatic clear cell RCC, I didn’t put the IMDC risk score, [and asked] what’s your ideal combination? A lot of you said…[we] need more data. I put the 4 combinations that have no less benefit…there was no 1 combination that [resulted in] 50% or higher. That’s why you need more, I would say, nuances.

I would say a patient that has a significant disease burden progressing quickly should have VEGF [inhibition and immunotherapy], I wouldn’t do any follow up with nivolumab [plus] ipilimumab [Yervoy] on them. They need a high response. I would say patients who have significant sarcomatoid differentiation, we’ve seen 19% [complete response] with nivolumab/ipilimumab, should go there. For Bone metastasis [and] brain metastases, we’re seeing some retrospective studies and in some of the prospective subgroup analyses that cabozantinib may have a role there. If say I’m a person that only believes in the longest PFS irrespective, well the longest PFS is [with lenvatinib (Lenvima) plus pembrolizumab (Keytruda)] at 24 months. There are nuances.

I remember my first review article when I was a starting fellow or a senior resident with Dr. Ron Bukowski was [about] the role of pegylated interferon and advanced RCC. I did the literature search, I think the paper was done in 3 or 6 [months], and the vast majority was in [patients with] hepatitis. That was where the inflammation was. We came all the way from single-agent [tyrosine kinase inhibitors] to immunotherapy single agents; now we’re combining [them and] patients with metastatic RCC are living way longer, years and years on average. If this is all the problem, what combination to pick, that’s fine. I think patients have options and patients with metastatic RCC live longer. And that’s the message today.


Motzer RJ, Choueiri TK, Powles T, et al. Nivolumab + cabozantinib (NIVO+CABO) versus sunitinib (SUN) for advanced renal cell carcinoma (aRCC): Outcomes by sarcomatoid histology and updated trial results with extended follow-up of CheckMate 9ER. J Clin Oncol. 2021;39(suppl 6):308. doi: 10.1200/JCO.2021.39.6_suppl.308