Expert Point of View: Sumanta K. Pal, MD

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Sumanta K. Pal, MD. ©Todd Buchanan 2018

Sumanta K. Pal, MD. ©Todd Buchanan 2018

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.

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