CheckMate 9ER Analysis: Potential Role for New Biomarker in Assessing aRCC Treatment

There is a potential role for protein fucsylation and sialylation mechanisms in driving resistance to nivolumab plus cabozantinib (NIVO+CABO) and sunitinib (SUN) in advanced renal cell carcinoma (aRCC), and serum glycoproteins involved in complement cascade and lipid metabolism that are predictive of response to NIVO+CABO versus SUN in aRCC have been identified, according to research presented at the European Society for Medical Oncology Congress 2024.

There is a need to better identify those who are most likely to benefit from either therapy, as not all patients experience a sustained response on either NIVO+CABO or SUN. Therefore, researchers led by David A. Braun, MD, PhD, aimed to investigate the protein glycosylation as a predictive prognostic biomarker of response to NIVO+CABO or SUN in aRCC using a novel liquid biopsy-based glycoproteomic platform.

Serum samples collected from 189 CheckMate 9ER participants treated with either NIVO+CABO or SUN were tested using a platform that combines high-resolution mass spectrometry with artificial intelligence and advanced machine learning.

Twenty-four glycopeptides were associated with PFS or OS for NIVO+CABO, whereas 64 glycopeptides were associated with PFS or OS for SUN. Participants with higher numbers of glucosyl modifications, including fucosylation and sialylation, had worse PFS and/or OS after treatment with NIVO+CABO and SUN, thus indicating their potential prognostic value (q-value<0.05).

Glycoproteins involved in the complement cascade and lipid metabolism were predictive of PFS response to NIVO+CABO vs SUN in Cox regression analysis (P<.01).

Among patients with high serum levels of complement protein 3 glycan at baseline, there was improved PFS with NIVO+CABO vs SUN (hazard ratio, 0.32; 95% CI, 0.14-0.69; P=.0025).