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

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 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 p p 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.