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

   

Authors:	Voss, M. H.; Chen, D.; Marker, M.; Hakimi, A. A.; Lee, C. H.; Hsieh, J. J.; Knox, J. J.; Voi, M.; Motzer, R. J.
Article Title:	Circulating biomarkers and outcome from a randomised phase II trial of sunitinib vs everolimus for patients with metastatic renal cell carcinoma
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.
Keywords:	survival; sorafenib; sunitinib; proteins; cytokine; renal cell cancer; biomarker; pazopanib; targeted therapy; everolimus; therapy; targeted; interferon-alpha; prognostic-factors; efficacy; 1st-line sunitinib
Journal Title:	British Journal of Cancer
Volume:	114
Issue:	6
ISSN:	0007-0920
Publisher:	Nature Publishing Group
Date Published:	2016-03-15
Start Page:	642
End Page:	649
Language:	English
ACCESSION:	WOS:000372523500007
DOI:	10.1038/bjc.2016.21
PROVIDER:	wos
PMCID:	PMC4800293
PUBMED:	26908330
Notes:	Article -- Source: Wos

https://synapse.mskcc.org/synapse/works/has_related_data_chk/92718