Identifying Reliable Biomarkers in Renal Cell Carcinoma

The CheckMate 9ER study (NCT03141177) investigated the role of protein glycosylation as predictive and prognostic biomarkers for response to nivolumab (Opdivo) and cabozantinib (Cabometyx) or sunitinib (Sutent) in patients with advanced renal cell carcinoma (aRCC). A novel glycoproteomic platform was used to analyze serum samples from 189 patients treated with nivolumab/cabozantinib or sunitinib in the CheckMate 9ER trial.

The analysis identified 24 glycopeptides associated with progression-free survival (PFS) in the nivolumab/cabozantinib arm and 64 glycopeptides associated with PFS or OS in the sunitinib arm. Higher levels of glucosyl modifications, including fucosylation and sialylation, were associated with worse PFS and/or OS in both treatment groups. Glycoproteins involved in complement cascade and lipid metabolism were found to be predictive of PFS response to nivolumab/cabozantinib vs sunitinib. Complement factor 3 glycan levels were particularly predictive, with patients having high levels showing improved PFS with nivolumab/cabozantinib compared to sunitinib.

These findings suggest that protein glycosylation mechanisms may play a role in driving resistance to nivolumab/cabozantinib and sunitinib in aRCC and that certain glycoproteins could serve as potential predictive biomarkers for treatment response.

Here, David Braun, MD, PhD, assistant professor of medicine and a member of the Center of Molecular and Cellular Oncology at Yale Cancer Center, goes further into the discussion of biomarkers in RCC.

Transcription:

0:05 | There's been a tremendous amount of work, and I would say huge progress, in deciphering genomic biomarkers, imaging-based biomarkers, transcriptomic biomarkers, even things at a single-cell resolution. So lots and lots of biomarkers in development, include circulating ones like KIM-1, but nothing yet that's actionable for the clinic.

0:24 | In my mind, with potentially one exception, which is probably the oldest one, which is looking under the microscope looking at tumors that have sarcomatoid histology. And that's really done histologically by looking at the morphology under microscope that really can predict from much better responses to immune therapy vs argeted therapy. So that's the one in my mind that really is the most actionable this time. The other are incredibly promising, but still steps away from the clinic.