Biomarkers defining probability of receiving second-line targeted therapy in metastatic renal cell carcinoma

Pawel Chrom,Cezary Szczylik,Maciej Kawecki,Lubomir Bodnar,Rafal Stec,Anna M Czarnecka

doi:10.1007/s12032-018-1148-x

Abstract

In order to facilitate long-term treatment decisions, we aimed to define biomarkers defining the probability of receiving second-line (SL) targeted therapy (TT) in patients with metastatic renal cell carcinoma (mRCC) based on their characteristics present at first-line TT initiation. We analysed 152 consecutive mRCC patients treated and used multivariable binominal logistic regression to identify factors contributing to the probability of receiving SL TT. Final model was assessed with bias-corrected indices (Nagelkerke’s R2 and area under receiver operating characteristic curve [AUC]) and two bootstrap procedures were used for internal validation. Factors associated with the probability of SL TT eligibility were the presence of brain metastases (odds ratio [OR] 0.084, 95% confidence interval [CI] 0.010–0.707), number of metastatic sites (OR 0.740, 95% CI 0.575–0.953 per each site), platelet count (OR 0.971, 95% CI 0.947–0.997, per 104/ml), lactate dehydrogenase level (OR 0.952, 95% CI 0.910–0.997 per 10 units/l), and albumin concentration (OR 1.924, 95% CI 1.057–3.503 per 1 g/dl). We developed on-line calculator that enables practicing clinicians to estimate SL treatment probability (http://www.r-calc.com).

Highlights

Multiple antiangiogenic compounds including bevacizumab, sorafenib, sunitinib and pazopanib are first-line standard-of-care treatment options of metastatic renal cell carcinoma providing progression-free survival (PFS) benefit as proven in randomised phase III trials [1]
Four of them were associated with decreased probability of having second-line therapy: the presence of brain metastases, number of metastatic sites, platelet count and lactate dehydrogenase (LDH) level, while albumin concentration was associated with increased probability
The MRCCSECLINE calculator developed in our study may be a useful tool for clinicians to identify those metastatic renal cell carcinoma (mRCC) patients, who are unlikely to receive second-line treatment, and subsequently, to help determine the most optimal, longterm treatment plan at the beginning of systemic targeted therapies (TT)

Summary

Introduction

Multiple antiangiogenic compounds including bevacizumab (anti- vascular endothelial growth factor [VEGF] antibody), sorafenib, sunitinib and pazopanib (tyrosine kinase inhibitors [TKIs] targeting VEGF receptors) are first-line standard-of-care treatment options of metastatic renal cell carcinoma (mRCC) providing progression-free survival (PFS) benefit as proven in randomised phase III trials [1]. These antiangiogenic therapies rarely provide complete or long-term responses [2]. Majority of patients in SL are treated with everolimus (40–60%) or sorafenib (up to 30%) [11, 12]

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