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The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study - 03/03/15

Doi : 10.1016/S1470-2045(14)71222-7 
Jenny J Ko, MD a, *, Wanling Xie, MS b, *, Nils Kroeger, MD c, Jae-lyun Lee, MD d, Brian I Rini, MD e, Jennifer J Knox, MD f, Georg A Bjarnason, MD g, Sandy Srinivas, MD h, Sumanta K Pal, MD i, Takeshi Yuasa, MD j, Martin Smoragiewicz, MD k, Frede Donskov, MD l, Ravindran Kanesvaran, MD m, Lori Wood, MD n, D Scott Ernst, MD o, Neeraj Agarwal, MD p, Ulka N Vaishampayan, MD q, Sun-young Rha, MD r, Toni K Choueiri, MD b, †, Daniel Y C Heng, DrMD a, ⁎, †
a Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada 
b Dana-Farber Cancer Institute, Boston, MA, USA 
c Department of Urology, University Hospital Greifswald, Ernst Moritz Arndt University, Greifswald, Germany 
d Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea 
e Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA 
f Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada 
g Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada 
h Division of Oncology, Stanford Medical Center, Stanford, CA, USA 
i City of Hope Comprehensive Cancer Center, Medical Oncology & Experimental Therapeutics, Duarte, CA, USA 
j Department of Urology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan 
k Department of Medical Oncology, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada 
l Department of Oncology, Aarhus University Hospital, Aarhus, Denmark 
m Division of Medical Oncology, National Cancer Centre Singapore, Singapore 
n Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS, Canada 
o London Regional Cancer Centre, London, ON, Canada 
p University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA 
q Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA 
r Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea 

* Correspondence to: Dr Daniel Y C Heng, Tom Baker Cancer Center, Alberta Health Services Cancer Care, University of Calgary, Calgary, AB T2N 4N2, Canada

Summary

Background

Previous prognostic models for second-line systemic therapy in patients with metastatic renal cell carcinoma have not been studied in the setting of targeted therapy. We sought to validate the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in patients with metastatic renal cell carcinoma receiving next-line targeted therapy after progression on first-line targeted therapy.

Methods

In this population-based study, we analysed patients who received second-line targeted therapy for metastatic renal cell carcinoma at 19 centres in Canada, USA, Greece, Japan, Singapore, South Korea, and Denmark. The primary endpoint was overall survival since the initiation of second-line therapy. We compared the prognostic performance of the IMDC model with the three-factor MSKCC model used for previously treated patients for overall survival since the start of second-line targeted therapy.

Findings

Between Jan 1, 2005, and Nov 30, 2012, we included 1021 patients treated with second-line targeted therapy. Median overall survival since the start of second-line targeted therapy was 12·5 months (95% CI 11·3–14·3). Five of six predefined factors in the IMDC model (anaemia, thrombocytosis, neutrophilia, Karnofsky performance status [KPS] <80, and <1 year from diagnosis to first-line targeted therapy) were independent predictors of poor overall survival on multivariable analysis. The concordance index using all six prognostic factors (ie, also including hypercalcaemia) was 0·70 (95% CI 0·67–0·72) with the IMDC model and was 0·66 (95% CI 0·64–0·68) with the three-factor MSKCC model. When patients were divided into three risk categories using IMDC criteria, median overall survival was 35·3 months (95% CI 28·3–47·8) in the favourable risk group (n=76), 16·6 months (14·9–17·9) in the intermediate risk group (n=529), and 5·4 months (4·7–6·8) in the poor risk group (n=261).

Interpretation

The IMDC prognostic model can be applied to patients previously treated with targeted therapy, in addition to previously validated populations in first-line targeted therapy. The IMDC prognostic model in the second-line targeted therapy setting has an improved prognostic performance and is applicable to a more contemporary patient cohort than that of the three-factor MSKCC model.

Funding

DF/HCC Kidney Cancer SPORE P50 CA101942-01, Kidney Cancer Research Network of Canada, Canadian Institute for Health Research, Trust Family, Loker Pinard, Michael Brigham, and Gerald DeWulf.

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