Original article
Clinical and laboratory prognostic factors in patients with metastatic renal cell carcinoma treated with sunitinib and sorafenib after progression on cytokines

https://doi.org/10.1016/j.urolonc.2013.09.011Get rights and content

Abstract

Objectives

The aim of this retrospective study was to analyze prognostic factors in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors (TKIs) sunitinib or sorafenib after progression on cytokine therapy.

Materials and methods

A national database of patients treated with targeted agents was used as the data source. A total of 319 patients treated with sunitinib (n = 181) or sorafenib (n = 138) after progression on cytokine therapy were analyzed.

Results

Prognostic factors significantly associated with poor overall survival in a multivariable Cox model included the time from diagnosis to the start of treatment with TKIs<1 year, increased neutrophil counts, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status 2 or higher. The parameters showing statistically significant association with progression-free survival included time from diagnosis to the beginning of treatment with TKI<1 year, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status 2 or higher. We have also validated the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model in our cohort of patients.

Conclusion

We demonstrate that the International Database Consortium prognostic model performs well for European patients treated with TKIs, including sunitinib or sorafenib, after progression on cytokines and suggest that a reduction from original 6 down to 4 parameters is possible.

Introduction

Prognostic scores play an important role in the management of patients with metastatic renal cell carcinoma (mRCC). All major randomized trials that established the activity of currently available targeted agents used a prognostic score as one of the principal inclusion or stratification criteria or both. The Memorial Sloan-Kettering Cancer Center (MSKCC) model introduced in 1999 is still widely used with minor modifications [1], [2], [3]. More recently, Heng and collaborators from the International Metastatic Renal-Cell Carcinoma Database Consortium (IDC) developed another prognostic model for patients treated with agents targeting the vascular endothelial growth factor pathway [4]. Prognostic models for mRCC that have been accepted for use in the clinical practice are summarized in Table 1. Although the IDC prognostic model has not been used in any major randomized trial, somewhat controversially it forms the basis for patient stratification in the 2012 European Society for Medical Oncology guidelines for mRCC treatment [5].

The present retrospective study has been designed to test the IDC model in a relatively homogeneous cytokine-pretreated population of patients with mRCC treated with targeted therapies including sunitinib (Pfizer) or sorafenib (Bayer) or both. Cytokines may still represent an option in a subgroup of patients and are used widely in resource-poor medical systems [6]. In addition, patients pretreated with cytokines are routinely analyzed together with those treated with first-line targeted agents in mRCC trials [7], [8].

Section snippets

Patients

Patients treated between June 2007 and April 2012 after progressing on cytokine therapy were included in the present registry-based retrospective analysis. RENIS (RENal Information System, http://renis.registry.cz) is a Czech database of patients with mRCC treated with targeted agents in comprehensive cancer centers [9]. Anonymized entries contain detailed standardized data on baseline characteristics, disease course, and therapy. The data is updated biannually. The registry is estimated to

Baseline characteristics, treatment, and survival

A total of 319 patients treated with sunitinib or sorafenib after progression on cytokines were analyzed, of which 138 received sorafenib, and 181 received sunitinib (Table 2). Out of the 319 patients, 309 (96.9%) patients had clear cell histology, 257 (81.3%) patients had previously received only IFN-α monotherapy, and 281 (88.1%) had undergone prior nephrectomy. As of the date of analysis, 76 (24%) patients were alive and without progression, 27 (8%) patients died before disease progression

Discussion

The present registry-based analysis identified the time from diagnosis to the start of TKI treatment of<1 year, increased ANC, increased LDH, and ECOG PS 2 or higher as independent predictors of OS in patients presenting for second-line TKI therapy. These prognostic parameters overlap to a large extent with the prognostic factors proposed by Heng et al. [4].

Historically, several prognostic systems have been proposed for mRCC, often reflecting the many changes occurring in the treatment

Acknowledgments

We would like to thank the following heads of the comprehensive cancer centers for their permission to use data of patients from their respective regional networks: Professor Jitka Abrahamova, Prague; Dr. Václav Janovský, České Budějovice; Professor Jindřich Fínek, Plzen; Professor Jiří Vorlíček, Brno; Dr. Lubomír Slavíček, Jihlava; Professor Renata Soumarová, Nový Jičín; Dr Jiří Bartoš, Liberec; Dr. David Feltl, Ostrava; Dr. Jana Prausová, Prague; Dr. Milan Lysý, Ústí nad Labem; Dr. Milan

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    T.B. has received honoraria for lectures from Bayer and Pfizer. I.K. has participated on advisory board for Bayer. K.K. has received travel grants and lecture fees from Bayer and Pfizer. B.M. has received honoraria for lectures from Bayer.

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