Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2016 Mar 15;114(6):642-9.
doi: 10.1038/bjc.2016.21. Epub 2016 Feb 23.

Circulating biomarkers and outcome from a randomised phase II trial of sunitinib vs everolimus for patients with metastatic renal cell carcinoma

Martin H Voss  1 , David Chen  2 , Mahtab Marker  2 , A Ari Hakimi  1 , Chung-Han Lee  1 , James J Hsieh  1 , Jennifer J Knox  3 , Maurizio Voi  2 , Robert J Motzer  1
Affiliations
Clinical Trial

Circulating biomarkers and outcome from a randomised phase II trial of sunitinib vs everolimus for patients with metastatic renal cell carcinoma

Martin H Voss et al. Br J Cancer. .

Abstract

Background: RECORD-3 assessed non-inferiority of progression-free survival (PFS) with everolimus vs sunitinib in previously untreated patients with metastatic renal cell carcinoma. Baseline plasma sample collection and randomised design enabled correlation of circulating biomarkers with efficacy.

Methods: Samples were analysed for 121 cancer-related biomarkers. Analyses of biomarkers categorised patients as high or low (vs median) to assess association with first-line PFS (PFS1L) for each treatment arm. A composite biomarker score (CBS) incorporated biomarkers potentially predictive of PFS1L with everolimus.

Results: Plasma samples from 442 of the 471 randomised patients were analysed. Biomarkers were associated with PFS1L for everolimus alone (29), sunitinib alone (9) or both (12). Everolimus-specific biomarkers (CSF1, ICAM1, IL-18BP, KIM1, TNFRII) with hazard ratio ⩾ 1.8 were integrated into a CBS (range 0-5). For CBS low (0-3, n = 291) vs high (4-5, n = 151), PFS1L differed significantly for everolimus but not for sunitinib. There was no significant difference in PFS1L between everolimus and sunitinib in the high CBS patient cohort.

Conclusions: Baseline levels of multiple soluble biomarkers correlated with benefit from everolimus and/or sunitinib, independent of clinical risk factors. A similar PFS1L was observed for both treatments among patients with high CBS score.

PubMed Disclaimer

Conflict of interest statement

MH Voss received research grants from BMS and Pfizer, advisory compensation from Novartis, Bayer, Calithera, Natera and Glaxo Smith Kline, and honoraria fees from Novartis. D Chen is an employee and stockholder of Novartis Pharmaceuticals Corp. M Marker is an employee and stockholder of Novartis Pharmaceuticals Corporation. JJ Hsieh has received research grants and advisory fees from Novartis. M Voi is an employee of Novartis Pharmaceuticals Corporation and a stockholder with Novartis, Pfizer and Bristol-Myers Squibb. RJ Motzer received research grants from Novartis, Pfizer, BMS, GlaxoSmithKline and Genentech and advisory compensation from Novartis and Pfizer. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study procedure. (A) Patient and biomarker population. (B) Development of composite biomarker score. EVE=everolimus; HR=hazard ratio; PFS1L=progression-free survival first line.
Figure 2
Figure 2
Kaplan–Meier curves for CBS high compared with low within treatment arms. CBS=composite biomarker score; PFS=progression-free survival.
See this image and copyright information in PMC

References

    1. Armstrong AJ, George DJ, Halabi S (2012) Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin. J Clin Oncol 30(27): 3402–3407. - PubMed
    1. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B 57(1): 289–300.
    1. Deprimo SE, Bello CL, Smeraglia J, Baum CM, Spinella D, Rini BI, Michaelson MD, Motzer RJ (2007) Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins. J Transl Med 5: 32. - PMC - PubMed
    1. Gerlinger M, Horswell S, Larkin J, Rowan AJ, Salm MP, Varela I, Fisher R, McGranahan N, Matthews N, Santos CR, Martinez P, Phillimore B, Begum S, Rabinowitz A, Spencer-Dene B, Gulati S, Bates PA, Stamp G, Pickering L, Gore M, Nicol DL, Hazell S, Futreal PA, Stewart A, Swanton C (2014) Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing. Nat Genet 46(3): 225–233. - PMC - PubMed
    1. Harmon CS, DePrimo SE, Figlin RA, Hudes GR, Hutson TE, Michaelson MD, Négrier S, Kim ST, Huang X, Williams JA, Eisen T, Motzer RJ (2014) Circulating proteins as potential biomarkers of sunitinib and interferon-alpha efficacy in treatment-naive patients with metastatic renal cell carcinoma. Cancer Chemother Pharmacol 73(1): 151–161. - PMC - PubMed

Publication types