Manuela Schmidinger, MD
FORMAL DISCUSSANT, Manuela Schmidinger, MD, of the Medical University of Austria, Vienna, commented on the CheckMate 214 findings. “We have just seen a change in the paradigm in the treatment of metastatic renal cell cancer.”
“More than a decade ago, VEGF [vascular endothelial growth factor] inhibitors were established as a new standard of care, and all three strategies listed in the ESMO [European Society for Medical Oncology] guidelines use VEGF inhibitors. However, all the first-line agents were approved based on significant benefits in progression-free survival and overall response rate, but not overall survival,” she told listeners.
Dr. Schmidinger continued: “So far, sunitinib [Sutent] has never been defeated by another treatment. Sunitinib is a brave comparator. Nivolumab [Opdivo] and ipilimumab [Yervoy] can be considered a new standard of care because of the survival benefit. The response rate is one of the highest seen in advanced [renal cell carcinoma], and the complete response rate is the highest ever seen.”
She pointed out that risk categories are not always clear-cut and that it is not always clinically evident that a patient is at favorable vs intermediate risk. Some guidelines lump favorable and intermediate risk together, so it may not be clear which is the best therapy to use first line.
Dr. Schmidinger considered the results associating PD-L1 [programmed cell death ligand 1] expression with outcomes as hypothesis-generating. “The value of PD-L1 as a predictive marker remains unclear. PD-L1–negative patients benefit from the combination of nivolumab and ipilimumab. The optimal cutoff point for PD-L1 expression and the best site for testing remain to be resolved.” ■
DISCLOSURE: Dr. Schmidinger has received honoraria for lectures and/or advisory boards from Pfizer, Novartis, Roche, BMS, Exelixis, Ipsen, Eisai, Astellas, and AstraZeneca.