Dr Braun on Frontline Nivolumab Monotherapy Followed by Salvage Nivolumab/Ipilimumab in RCC

David A. Braun, MD, PhD, assistant professor of Medicine (Medical Oncology), Louis Goodman and Alfred Gilman Yale Scholar, Yale Cancer Center and Smilow Cancer Hospital, Yale School of Medicine, discusses the rationale for evaluating frontline nivolumab (Opdivo) and salvage nivolumab plus ipilimumab (Yervoy) in patients with advanced renal cell carcinoma (RCC) in the phase 2 HCRN GU16-260 trial (NCT03117309).

The HCRN GU16-260 study aimed to further address the use of immunotherapy in the first-line treatment of RCC, Braun beings. Investigators sought to identify whether nivolumab could be effective as a single agent in the frontline setting, and during the study, all patients received nivolumab monotherapy. Cohort A included patients with clear cell RCC, and Cohort B featured patients with non–clear cell histology.

Patients who achieved a complete or partial response continued on single-agent nivolumab maintenance. Those who had either progressive or stable disease continued to part B of the study, where they were given 4 cycles of nivolumab plus ipilimumab, followed by nivolumab maintenance.

Nivolumab plus ipilimumab has been established as an effective frontline regimen in advanced kidney cancer; however, investigators of this study aimed to understand if patients can be treated with these agents sequentially, Braun says. By treating with nivolumab monotherapy first, responders could be spared treatment with a second agent in the frontline setting, Braun notes.

Although data from the trial demonstrated that there was some activity for nivolumab monotherapy, and some patients that may have been rescued with ipilimumab later, the bulk of data indicate that nivolumab/ipilimumab is best used as an up-front combination treatment, rather than sequential treatment, Braun explains.

This phase 2 trial was unique because it provided an opportunity for detailed tumor specimen collection to enable conventional exome sequencing and bulk RNA sequencing, he explains. Investigators hope to use these samples to better understand the biology of RCC and ultimately identify patients more likely to responded to immune checkpoint inhibitors, Braun concludes.