Over the past 12 years, “the debates in kidney cancer have gotten more exciting. Combination therapy with a programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitor is an area of intense study,” said formal discussant and ASCO Expert Sumanta K. Pal, MD, of City of Hope, Duarte, California.
“This is a banner year for immunotherapy in renal cell carcinoma,” he added. “Checkmate 214 showed an impressive survival benefit for nivolumab (Opdivo) plus ipilimumab (Yervoy) over sunitinib (Sutent) in intermediate- and poor-risk patients. Treatment-related adverse event rates were higher with the combination, and more toxic deaths were seen. Also, 60% required corticosteroids for immune-related adverse events. However, a sizable difference [in benefit] was seen favoring PD-L1–positive patients, so I don’t think the PD-L1 story is over in the context of nivolu-mab plus ipilimumab,” Dr. Pal said.
The IMmotion 151 trial also represented topline data favoring atezolizumab (Tecentriq)/bevacizumab (Avastin) in both PD-L1–positive and intent-to-treat populations. This suggests that PD-L1 status cannot be used to select patients for this therapy, he noted.
Higher Plateau Effect
“The goal of combination therapy is to take the protracted progression-free survival seen with tyrosine kinase inhibitors and combine that with the plateau effect we see with immune-oncology–based therapy, to achieve a higher plateau in terms of durable responses,” Dr. Pal explained.
“Dr. Atkins’ study showed very impressive response rates with axitinib/pembrolizumab, and the real addition of this data set is the durability. An 18.6-month duration of response and a median progression-free survival of 21 months—this is unprecedented,” he stated.
“Multiple other regimens being studied in the landscape, including cabozantinib (Cabometyx)/nivolumab with or without ipilimumab, tivozanib plus nivolumab, and others. Across all combinations, response rates are around 75%, and clinical benefit approaches 100%. The question is: Will these studies play out and show that patients are living longer?” Dr. Pal continued.
“It is still possible that a subset of patients can get away with monotherapy with either immunotherapy or a VEGFR inhibitor. In the future, we will build on the front-line success of immunotherapy. We still have not resolved the PD-L1 story,” he added. ■
DISCLOSURE: Dr. Pal reported no conflicts of interest.
The combination of axitinib (Inlyta) plus pembrolizumab (Keytruda) can be added to the list of combination therapies that look promising in advanced renal cell carcinoma. In a phase Ib trial, almost three-quarters of patients with newly diagnosed advanced renal cell carcinoma treated with the...