Immune-high and stromal-low signatures were associated with response to nivolumab among patients with advanced clear cell renal cell carcinoma (ccRCC), according to an analysis presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

“These findings pave the way for the development of a clinically available IHC [immunohistochemistry] predictive tool,” Maxime Meylan of the Sorbonne Université in France, and presenter of the study, said.

The NIVOREN GETUG-AFU 26 trial evaluated the safety and efficacy of nivolumab treatment in 720 patients with metastatic ccRCC. This analysis included 324 patients from the larger population to determine if gene expression signatures could serve as a predictive biomarker for outcomes associated with nivolumab treatment.

Primary ccRCC specimens were formalin-fixed and paraffin-embedded; 324 specimens were available for IHC and 184 were available for RNA sequencing. The study included a discovery phase, in which signatures for T effectors and angiogenesis and kidney ccRCC immune classification (KIC) were generated, followed by a validation phase to confirm associations with outcomes.


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Among the 79 patients and corresponding specimens used for the discovery phase, both T effector and angiogenesis signatures were associated with outcomes with nivolumab. The combination of a low angiogenesis signature and a high T effector signature was associated with higher objective response rate (ORR) and longer progression-free survival (PFS) with nivolumab, whereas the poorest ORR and PFS were associated with low signatures for T effectors and angiogenesis.

Five KICs were identified using the discovery cohort. There was a 31% overlap between KIC immune-high/stromal-high and the angiogenesis low/T effector high signatures, suggesting that these markers “mostly identified different tumors,” Dr Meylan said.

KIC immune-high/stromal-low was associated with improved ORR and PFS with nivolumab in the discovery cohort. This was confirmed with the validation cohort, in which the KIC immune-high/stromal-low cohort had an ORR of 36% compared with 13% with other KIC subtypes.

Dr Meylan concluded that “the KIC immune-high/stromal-low signature is driven by an abundance of CD8 T cells, B cells/neutrophils, fibroblasts, endothelial cells, respectively.”

Disclosures: Multiple authors declared affiliation with industry. Please refer to the original abstract for a full list of disclosures.

Reference

Meylan M, Beuselinck B, Dalban C, et al. Kidney ccRCC immune classification (KIC) enhances the predictive value of T effector (Teff) and angiogenesis (Angio) signatures in response to nivolumab (N). Presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract 700O.

This article originally appeared on Cancer Therapy Advisor