Circulating biomarkers and outcome from a randomised phase II trial of sunitinib vs everolimus for patients with metastatic renal cell carcinoma |
| |
Authors: | Martin H Voss David Chen Mahtab Marker A Ari Hakimi Chung-Han Lee James J Hsieh Jennifer J Knox Maurizio Voi Robert J Motzer |
| |
Affiliation: | 1.Memorial Sloan Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA;2.Novartis Oncology, One Health Plaza, East Hanover, NJ 07936-1080, USA;3.Princess Margaret Cancer Center, University of Toronto, 5-210, 610 University Avenue, Toronto, Ontario M5G-2M9, Canada |
| |
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: | renal cell cancer targeted therapy biomarker sunitinib everolimus |
|
|