Background: Limited data exist on outcomes for metastatic renal cell carcinoma (mRCC) patients treated with multiple lines of therapy. Overall survival of individuals who received 1, 2, or 3+ lines of TT were 14.9, 21.0, and 39.2 months, respectively, from first-line TT (12.4 months from 2006 to 2008 (Wahlgren (ADAPT; ClinicalTrials.gov Identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT01582672″,”term_id”:”NCT01582672″NCT01582672); Individuals who received first-line TT and previously underwent nephrectomy, much like those enrolled in (TIVO-1; ClinicalTrials.gov Identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT01030783″,”term_id”:”NCT01030783″NCT01030783); Individuals who received second-line TT after at least one other VEGF- TT, much like those enrolled in (INTORSECT; ClinicalTrials.gov Identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT00474786″,”term_id”:”NCT00474786″NCT00474786); All individuals who received third-line therapy; Individuals who received third-line TT and were previously exposed to one VEGF inhibitor and one mTOR inhibitor, much like those enrolled in (Platinum; ClinicalTrials.gov Identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT01223027″,”term_id”:”NCT01223027″NCT01223027). For each subgroup, we acquired the median OS and PFS, determined from your line of therapy under consideration unless normally specified. We defined OS as the period between TT initiation and day of death, unless it was censored on the day of the last follow-up check out. We defined PFS as the period between treatment initiation and progression, drug cessation, or death, unless it was censored in the last follow-up check out. Progression was assessed radiologically using the Response Evaluation Criteria in Solid Tumors (RECIST), or clinically when continuation of treatment was deemed futile (Eisenhauer et al, 2009). Statistical analysis Baseline individual and disease characteristics were summarised using descriptive analysis. Overall survival and PFS were estimated for each sub-cohort having a 95% confidence interval (CI), and variations among the sub-cohorts were adjusted from the known self-employed predictors of poorer OS (KPS <80%, analysis to treatment interval <1 yr, hypercalcemia, anemia, thrombocytosis, neutrophilia) using proportional risks regression (Heng et al, 2009). The statistical analyses were performed using SAS version 9 (SAS Institute, Cary, NC, USA), and P<0.05 (two-sided) was considered statistically significant. Results Patient and treatment Rabbit Polyclonal to DHRS4 characteristics In total, 2705 individuals were included in the study cohort having a median follow-up period of 37 weeks. Their baseline patient characteristics and therapies are summarised in Table 1. One thousand five hundred and thirty three individuals (57%) received or are still receiving 1TT. The most frequently used first-line therapy was sunitinib, used in 1959 individuals (72%). This was followed by sorafenib in 474 individuals (18%) and bevacizumab in 109 individuals (4%). Additional first-line choices included temsirolimus, pazopanib, everolimus, and axitinib. In total, 734 individuals (27%) received a total of two lines of therapy, whereas only 438 individuals (16%) received three or more lines of therapy. Table 1 Baseline patient characteristics Survival results in the IMDC cohort The median OS in individuals who received only one TT was 14.9 months from the time of first-line therapy initiation (95% CI, 13.2C16.7 months), with PFS of 6.7 months (95% CI, 5.9C7.5 months). In contrast, the median OS in individuals who received two lines of therapy was 21.0 months, measured from the time of first-line therapy initiation (95% CI, 19.1C23.5 months), with PFS of 3.4 months, measured from the time of second-line therapy initiation (95% CI, 3.0C3.9 months). Individuals who received three or more lines of TT experienced an OS of 39.2 months, measured from the time of first-line initiation (95% CI, 36.3C41.9 months), with PFS of 4 months, measured from the time of third-line therapy initiation (95% CI, 3.4C4.5 months). On multivariable analysis, modifying for the IMDC prognostic criteria, receiving second-line or third-line therapy was individually associated with better OS (HR=0.738, 95% CI 0.663C0.821; HR=0.626, 95% CI 0.541C0.724, respectively, both P<0.0001). Table 2 summarises the survival outcomes of the six subgroups, as explained above. Table 2 OS and PFS in the specified sub-cohorts using data from your IMDC (observe Materials and Methods) Discussion Survival benchmark studies provide context when designing and interpreting fresh clinical trials. Results from real-life cohorts treated with current standard therapies serve as comparators for long term clinical trials, with the 61413-54-5 expectation that newer therapies will perform better than the standard therapies. The benchmarked results can also allow for future statistical considerations such as sample size for fresh prospective tests. Prior benchmark studies in mRCC were limited to 61413-54-5 individuals who received cytokine immunotherapy (Belldegrun et al, 2008). Since the initial Food and Drug Administration (FDA) authorization of sorafenib in 2005, contemporary targeted treatments have now mainly replaced immunotherapy as the new standard of care. This study is, to the authors’ knowledge, the 1st and largest multi-national 61413-54-5 benchmarking study to day of mRCC individuals treated with at least one line of TT. One of the limitations in our strategy is definitely its retrospective individual recruitment. Individuals included in our cohort were not selected on a certain criteria or hand-picked by each 61413-54-5 centre; rather, they were derived from consecutive patient lists in pharmacy or registry data. This strategy was employed.