Predictive value of C reactive protein (CRP) in patients with metastatic renal cell carcinoma (mRCC) treated with pembrolizumab (pembro) and axitinib (axi).
Authors: Qaisar Aitzaz , Venugopal Balaji , Ansel Sonam , Jones Robert J. , Slater Sarah , Symeonides Stefan N. , Malik Jahangeer , Sundaramurthy Aravindhan , Elliott Tony , Devasar Abeera , Stares Mark , Randhawa Manreet 
Published: March 2023

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Background: CRP, a biomarker of systemic inflammation, has been shown to have prognostic value in numerous tumour types, including mRCC. The combination of the immune check inhibitor (ICI), pembro, and vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) axi is one of several internationally approved combination ICI/VEGFR-TKI treatment options. We evaluated the predictive value of biomarkers of systemic inflammation in a real-world cohort of patients with mRCC treated with pembro and axi. Methods: Retrospective data of patients treated with pembro and axi were collected from a regional electronic database from two large cancer centres. Inflammatory biomarkers from routine blood tests (including haemoglobin, neutrophil count, platelets, albumin and CRP) prior to starting treatment were recorded. The IMDC score and modified Glasgow Prognostic Score (combining albumin and CRP) were calculated. The primary end point, progression free survival (PFS), was defined as the time between initiation of treatment and clinical or radiographical progression or death, or censorship. Overall survival, defined as the time between initiation of treatment and death, or censorship was also calculated. Univariate and multivariate analyses were undertaken using Cox Regression model and the relationship between different markers and PFS was assessed using Kaplan-Meier curves. Results: Data were available for 93 patients. 74 pts (80%) had clear cell histology, 19 pts (20%) had non-clear cell and 11 pts (12%) had sarcomatoid component. 46 patients had previous nephrectomy. 15 (16%), 46 (50%) and 32 (34%) pts respectively were classified as favourable, intermediate, and poor risk group as per IMDC score. Median PFS was 10.7 (IQR 4.6-not reached) months after a minimum 12.5 months follow-up. Baseline CRP was recorded in 77 (83%) patients, reflecting current routine clinical guidelines. On univariate analysis, neutrophils (≤7.5x109/L/>7.5x109/L) (p=0.044), platelets (≤400 x109/L/>400x109/L) (p=0.043), CRP (≤10mg/L/>10mg/L) (p=0.001), mGPS (0/1/2) (p=0.004) and IMDC risk group (low/intermediate/poor) (p=0.038) were predictive of PFS. On multivariate analyses only CRP was associated with PFS (HR2.78 (95% CI, 1.42-5.44) (p=0.003). At a 1-year landmark PFS was 62% (CRP ≤10mg/L) v 29% (CRP >10mg/L) (p=0.002). CRP also predicted OS ((HR4.50 (95% CI, 1.58-12.8) (p=0.005)) with 1-year OS 85% (CRP ≤10mg/L) v 59% (CRP >10mg/L) (p=0.002). Conclusions: CRP, a biomarker of systemic inflammation, predicts survival in mRCC patients undergoing combined ICI/VEGF-TKI therapy. Our findings support comparable studies in the mRCC population and routine recording of CRP in patients with mRCC. We advocate further work to validate utilisation of CRP as a prognostic biomarker for mRCC in clinical practice.