ASCO GU 2020: NIVOREN GETUG-AFU 26 Translational Study: Association of PD-1, AXL, and PBRM-1 with Outcomes in Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Nivolumab

San Francisco, California (UroToday.com) The NIVOREN GETUG-AFU26 trial was a phase II multicenter prospective French study evaluating the efficacy and safety of nivolumab administered to patients with metastatic renal cell carcinoma after failure of 1 or 2 tyrosine kinase inhibitors, a so called “real world” setting. The final results from this study were presented in 2019 at GU ASCO and summarized here. This study showed comparable outcomes to CheckMate-025 testing nivolumab versus everolimus in pre-treated metastatic RCC.

Multiple efforts are underway to identify robust biomarkers of response to nivolumab. The framework for biomarker analysis is shown below:

ASCOGU_NIVOREN_GETUG-AFU26.png

In this presentation, the authors reported the associations of outcome with expression of the epithelial to mesenchymal transition marker AXL, checkpoint molecules PD1/TIM3/LAG3, and SWI/SNF proteins BAP1 and PBRM1.

Of the checkpoint molecules, higher PD1 expression than the median at the invasive tumor margin was associated with a statistically significant difference in progression free survival (HR = 0.67, p = 0.04) but not overall survival (HR = 0.96, p = 0.9). TIM3 expression in either the immune infiltrate or tumor was not associated with PFS or OS. Quartile 3 or higher expression of LAG3 was numerically associated with worsened OS, but this was not statistically significant (HR 1.44, p = 0.1)

Approximately 45% of tumor cells assay showed AXL expression. Any tumor with an expression of AXL had worse progression free survival (2.9 months relative to 5 months, HR 1.29, p= 0.04), but no difference in overall survival.

With regards to SWI/SNF proteins, loss of PBRM1 protein expression was associated with a numerical but not statistically significant higher progression free survival (5.3 months vs 3.9 months, HR = 0.75, p=0.1). Loss of PBRM1 expression was shown to confer a higher overall survival rate in this cohort at 12 months of follow-up (83.7% vs 74%, HR 0.59, p=0.05). BAP1 loss was not associated with either outcome parameter.

In conclusion, the authors presented specific biomarker reports from the NIVOREN GETUG-AFU 26 trial of nivolumab in metastatic clear cell renal cell cancer. Of the markers presented here, only PBRM1 loss was associated with improved overall survival at twelve months to a statistically significant extent. More integrated analysis of various molecular parameters from this study and subsequent prospective validation may provide greater insight into what patients will benefit from nivolumab.

Presented by: Yann-Alexandre Vano, MD, Department of Medical Oncology, Georges Pompidou Hospital, University Paris Descartes, Paris France

Written by: Alok Tewari, MD, PhD, Medical Oncology Fellow at the Dana-Farber Cancer Institute, at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California

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