A five-factor biomarker profile obtained week 4-12 of treatment for improved prognostication in metastatic renal cell carcinoma: Results from DARENCA study 2.

Autor: Soerensen AV; a Department of Oncology , Herlev Hospital, University of Copenhagen , Herlev , Denmark ., Geertsen PF; a Department of Oncology , Herlev Hospital, University of Copenhagen , Herlev , Denmark ., Christensen IJ; b The Finsen Laboratory , Rigshospitalet and Biotech Research and Innovation Centre (BRIC), University of Copenhagen , Copenhagen , Denmark ., Hermann GG; c Department of Urology , Rigshospitalet, University of Copenhagen , Copenhagen , Denmark ., Jensen NV; d Department of Oncology , Odense University Hospital , Odense , Denmark ., Fode K; e Department of Oncology , Aarhus University Hospital , Aarhus , Denmark ., Petersen A; f Department of Pathology , Aalborg University Hospital , Aalborg , Denmark , and., Sandin R; g Pfizer Oncology , Sollentuna , Sweden., Donskov F; e Department of Oncology , Aarhus University Hospital , Aarhus , Denmark .
Jazyk: angličtina
Zdroj: Acta oncologica (Stockholm, Sweden) [Acta Oncol] 2016; Vol. 55 (3), pp. 341-8. Date of Electronic Publication: 2015 Oct 08.
DOI: 10.3109/0284186X.2015.1091499
Abstrakt: Background: Several biomarkers of treatment efficacy have been associated with a better prognosis in patients with metastatic renal cell carcinoma (mRCC). The prognostic significance of biomarkers in the early treatment phase is unclear.
Material and Methods: In a complete national cohort of mRCC patients receiving first-line tyrosine kinase inhibitors (TKI) or interleukin-2 based immunotherapy (IT) from 2006 to 2010, overall survival (OS) was analysed for baseline International mRCC Database Consortium (IMDC) classification factors and on-treatment time-dependent biomarkers obtained day 1 each cycle week 4-12 after treatment initiation with multivariate analysis and bootstrap validation.
Results: A total of 735 patients received first-line TKI (59%) or IT (41%). Median OS was overall 14.0 months and 33.4, 18.5, and 5.8 months for baseline IMDC favourable, intermediate, and poor risk groups, respectively (p < 0.0001). Systolic blood pressure ≥140 mmHg, neutrophils < lower level of normal (LLN), platelets < LLN, sodium ≥ LLN, and LDH ≤1.5 times upper level of normal after treatment initiation were significantly associated with favourable OS independent of baseline IMDC risk group in multivariate analyses stratified for TKI and IT (p ≤ 0.04). Concordance (C)-index for IMDC classification alone was 0.625 (95% CI 0.59-0.66) and combined with the five-factor biomarker profile 0.683 (95% CI 0.64-0.72). For patients with good (3-5 factors) and poor (0-2 factors) biomarker profile median OS were 23.5 and 9.6 months, respectively (p < 0.0001). Adding the five-factor biomarker profile significantly improved prognostication in IMDC intermediate (25.7 vs. 12.0 months, p < 0.0001) and poor (12.8 vs. 6.4 months, p < 0.0001) risk groups. A trend was seen in IMDC favourable risk group (38.9 vs. 28.7 months, p = 0.112).
Conclusion: On-treatment hypertension, neutropenia, thrombocytopenia, LDH below 1.5 times upper level of normal, and normal sodium, obtained week 4-12 of treatment, are independent biomarkers of favourable outcome in mRCC, independent of treatment type.
Databáze: MEDLINE
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