Overall survival improvement in patients with metastatic clear-cell renal cell carcinoma between 2000 and 2020: a retrospective cohort study

Background Only a few recent phase III trials with targeted therapies or immune checkpoint inhibitors (ICIs) in metastatic clear-cell renal cell carcinoma (m-ccRCC) demonstrated an overall survival (OS) benefit compared to standard of care. We aimed to study the evolution of OS since the start of systemic therapy from 2000 to 2020. Patients and methods Retrospective study on all consecutively treated m-ccRCC patients in three Belgian hospitals starting with systemic therapy. The study outcome was OS since the start of systemic therapy. We used a univariable Cox model for OS with year of the start of therapy as a predictor, and a multivariable analysis including known prognostic factors. Linear and non-linear trends of time were tested. Results Five hundred patients were included. In a linear model, the HR for OS depending on the year of the start of therapy was 0.95 (95%CI 0.93-0.97; p < 0.0001), estimated for an increase with 1 year in time. In a non-linear model, OS started to improve from 2006 on, when vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) replaced interferon alfa (IFNa) as a standard of care and continued to increase steadily during the following years. On multivariable analysis, the year of the start of therapy remained an independent prognostic factor for OS. Two-year OS after the start of systemic therapy was 23%, 34%, 50% and 59% for patients who started treatment in 2000-2005, 2006-2011, 2012-2017, and 2018-2020, respectively. The five-year OS of the first three groups was 7%, 14% and 24%. The mean number of administered lines of therapy increased over time, with an incidence rate ratio of 1.07 (95%CI 1.05-1.08; p < 0.0001) per year increase for the period 2000-2016. Conclusion OS of m-ccRCC patients has been improving significantly over the last 15 years since the introduction of VEGFR-TKIs and ICIs.