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.British Journal of Cancer advance online publication, 23 February 2016; doi:10.1038/bjc.2016.21 www.bjcancer.com.
British journal of cancer. 2016 Feb 23 [Epub ahead of print]
Martin H Voss, David Chen, Mahtab Marker, A Ari Hakimi, Chung-Han Lee, James J Hsieh, Jennifer J Knox, Maurizio Voi, Robert J Motzer
Memorial Sloan Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA., Novartis Oncology, One Health Plaza, East Hanover, NJ 07936-1080, USA., Novartis Oncology, One Health Plaza, East Hanover, NJ 07936-1080, USA., Memorial Sloan Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA., Memorial Sloan Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA., Memorial Sloan Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA., Princess Margaret Cancer Center, University of Toronto, 5-210, 610 University Avenue, Toronto, Ontario M5G-2M9, Canada., Novartis Oncology, One Health Plaza, East Hanover, NJ 07936-1080, USA., Memorial Sloan Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA.