Michael R. Harrison, MD
There are potential practice-changing regimens on the horizon following exciting findings from the CABOSUN and CheckMate-214 trials for patients with advanced renal cell carcinoma (RCC).
In the CABOSUN study, frontline treatment with cabozantinib (Cabometyx) demonstrated superiority in progression-free survival (PFS) over sunitinib (Sutent) in patients with advanced RCC. Findings demonstrated that patients treated with cabozantinib had a median PFS of 8.6 months versus 5.3 months with sunitinib (HR, 0.66; 95% CI, 0.46-0.95; 1-sided P
The CheckMate-214 study compared the combination of ipilimumab (Yervoy) and nivolumab (Opdivo) with single-agent sunitinib as a first-line treatment for advanced or metastatic RCC. In patients with intermediate- and poor-risk disease, the median OS was not reached in the nivolumab/ipilimumab arm and was 26.0 months in the sunitinib arm (HR, 0.63; 99.8% CI, 0.44-0.89; P
Median PFS for the combination was 11.6 months versus 8.38 months for sunitinib (HR, 0.82; 99.1% CI, 0.64-1.05; P
“Ipilimumab and nivolumab in the population of intermediate- and poor-risk patients improved overall response rate and OS. However the PFS, although there was a trend towards improvement, was not statistically significant,” said Michael R. Harrison, MD.
In an interview with OncLive
during the 2017 State of the Science SummitTM
on Genitourinary Cancers, Harrison, an assistant professor of medicine, Department of Medicine, Duke University School of Medicine, Duke Cancer Institute, discussed emerging data that are likely to impact the treatment landscape for patients with RCC.
OncLive: Can you please provide an overview of your presentation?
My talk covered the sequencing of therapies for RCC—not only in metastatic RCC, but also in the localized setting. I discussed the S-TRAC trial, which investigated sunitinib for high-risk localized RCC. I then discussed the randomized phase II CABOSUN trial, which investigated cabozantinib versus sunitinib in intermediate- and poor-risk patients with metastatic RCC who were previously untreated. Lastly, I focused on the CheckMate-214 trial investigating ipilimumab and nivolumab combined versus sunitinib also in the intermediate and poor-risk population that was previously untreated.
In terms of the highlights, there is a portion of patients with localized RCC who have a relatively high risk of recurrence. This is about 15% of patients with localized RCC with the risk of recurrence by 5 years, which is roughly 60%. Until recently, there was no standard of care for this patient population. They were typically managed by observation alone.
The S-TRAC study is important in demonstrating a reduction in the risk of recurrence in this high-risk population versus observation alone. Specifically, there was an advantage in disease-free survival reduction of 24%.
In terms of the CABOSUN study and the CheckMate-214 study, I highlighted that cabozantinib did improve PFS versus sunitinib. This was a relatively small randomized phase II study. Ipilimumab and nivolumab in the population of intermediate- and poor-risk patients improved ORR and OS. However, the PFS, although there was a trend towards improvement, was not statically significant.
Putting all of this information together has been a challenge. These data are still very new and have not yet been published. We are still awaiting some answers, but the ipilimumab and nivolumab data are practice changing. That is going to be used in the frontline setting in a large portion of patients who have that intermediate- and poor-risk RCC.
A question that remains is, “What do we do after that?” There are studies already being designed to answer that question. There are also other studies on the heels of CheckMate-214 that are investigating combinations of checkpoint inhibitors with anti-VEGF strategies. The question then becomes, “Is it better to do a checkpoint combination versus a combination like sunitinib and VEGF receptor TKI, or is it better to combine a checkpoint inhibitor with an anti-VEGF therapy?"