JAVELIN Renal 101 complemented two other noteworthy trials exploring first-line checkpoint inhibitors for which new data were reported at the symposium. One, KEYNOTE-426 (NCT02853331), established that the combination of the immune checkpoint inhibitor pembrolizumab (Keytruda) and axitinib was superior to sunitinib. The other, CheckMate 214 (NCT02231749), established that the combination of two immune checkpoint inhibitors, nivolumab (Opdivo) and ipilimumab (Yervoy), was superior to sunitinib.
Weighing new options
“So a new standard of care in 2019 is present: The majority of patients with advanced clear cell RCC will be eligible to receive the combination of a checkpoint inhibitor and axitinib,” commented invited discussant Lori Wood, MD, a professor in the division of medical oncology at Dalhousie University, Halifax, Canada. “The questions now are: Which treatment should we choose? can we afford it? and perhaps more importantly, can we safely deliver this therapy to all patients?”
Dr. Lori Wood
When it comes to selecting among the three combinations above, “I don’t think PD-L1 expression is going to help us at all,” she said. In contrast, IMDC risk category is likely still helpful because, in CheckMate 214, there was no progression-free or overall survival benefit of ipilimumab/nivolumab in patients with favorable-risk disease.
Differences in rates of discontinuation of all treatment because of treatment-related adverse events are hard to assess because CheckMate 214 had restrictions on allowing patients in the combination group to receive single-agent nivolumab, according to Dr. Wood. Financial costs are a major consideration, but so are time and staffing costs: Compared with single-agent sunitinib, the combinations as much as triple physician visits, nurse visits, infusions, and unscheduled visits.
