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2016 ; 114
(6
): 642-9
Nephropedia Template TP
gab.com Text
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Circulating biomarkers and outcome from a randomised phase II trial of sunitinib
vs everolimus for patients with metastatic renal cell carcinoma
#MMPMID26908330
Voss MH
; Chen D
; Marker M
; Hakimi AA
; Lee CH
; Hsieh JJ
; Knox JJ
; Voi M
; Motzer RJ
Br J Cancer
2016[Mar]; 114
(6
): 642-9
PMID26908330
show ga
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.