Targeted Therapies in Advanced Renal Cell Carcinoma
Targeted Therapies in Advanced Renal Cell Carcinoma
We retrospectively collected clinical data of 366 consecutive patients with mRCC who received TTs as first-line or subsequent treatment lines at the Istituto Nazionale Tumori between January 2005 and October 2012. The study was approved by the local ethical committee. Patients with missing data regarding both OS and PFS end points were excluded from analysis; in total, 358 (97.8%) patients were available for evaluation. All the patients had histologically proven primary RCC and had received TT within a clinical trial (EU-ARCCS, TARGET, AVOREN or ROSORC), or in a clinical practice setting. TTs included: sunitinib 50 mg orally daily (4 weeks on and 2 weeks off), sorafenib 400 mg orally twice daily, bevacizumab 10 mg/kg intravenously every 2 weeks in combination with IFN-α, pazopanib 800 mg orally daily and temsirolimus 25 mg intravenously weekly.
Baseline data were analyzed by descriptive statistics. PFS was defined as the time from the start of first-line treatment to objective tumor progression or death (which ever occurred first); the progression of disease was evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1; patients who were alive and progression-free at the time of the last contact were right censored. OS was defined as the time from the start of first-line treatment to death for any cause; patients alive or lost to follow-up at the time of the last contact were right censored. The last update was performed in December 2012.
A multivariate Cox regression model was evaluated in order to test the association between metastatic sites and PFS and OS end points, and to estimate hazard ratios (HRs). In this model, metastatic sites were categorized as the liver, lungs, brain, bone and lymph, and other sites were introduced as binary predictors.
The same multivariate model, but with the Mozter score included as an ordinal predictor, was also evaluated. An univariate Cox regression model was evaluated in order to test the statistical association between the number of metastatic sites and PFS and OS end points, and to estimate the HR; in this model, the number of metastatic sites was introduced as a continuous predictor. The same univariate model with the Mozter score added as an ordinal predictor was evaluated.
Crude survival curves were estimated using the Kaplan–Meier method; adjusted survival curves were estimated using the mean of covariates method. The prevalence of each metastatic site was entered into both multivariate Cox regression models, in order to estimate the adjusted survival functions.
All statistical tests were two sided and a p-value of <0.05 was considered statistically significant. Statistical analysis was performed using the SAS software version 9.2 (SAS Institute, NC, USA); the adjusted survival functions were estimated and plotted using STATA software version 12.1 (StataCorp, TX, USA).
Patients & Methods
We retrospectively collected clinical data of 366 consecutive patients with mRCC who received TTs as first-line or subsequent treatment lines at the Istituto Nazionale Tumori between January 2005 and October 2012. The study was approved by the local ethical committee. Patients with missing data regarding both OS and PFS end points were excluded from analysis; in total, 358 (97.8%) patients were available for evaluation. All the patients had histologically proven primary RCC and had received TT within a clinical trial (EU-ARCCS, TARGET, AVOREN or ROSORC), or in a clinical practice setting. TTs included: sunitinib 50 mg orally daily (4 weeks on and 2 weeks off), sorafenib 400 mg orally twice daily, bevacizumab 10 mg/kg intravenously every 2 weeks in combination with IFN-α, pazopanib 800 mg orally daily and temsirolimus 25 mg intravenously weekly.
Statistical Methods
Baseline data were analyzed by descriptive statistics. PFS was defined as the time from the start of first-line treatment to objective tumor progression or death (which ever occurred first); the progression of disease was evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1; patients who were alive and progression-free at the time of the last contact were right censored. OS was defined as the time from the start of first-line treatment to death for any cause; patients alive or lost to follow-up at the time of the last contact were right censored. The last update was performed in December 2012.
A multivariate Cox regression model was evaluated in order to test the association between metastatic sites and PFS and OS end points, and to estimate hazard ratios (HRs). In this model, metastatic sites were categorized as the liver, lungs, brain, bone and lymph, and other sites were introduced as binary predictors.
The same multivariate model, but with the Mozter score included as an ordinal predictor, was also evaluated. An univariate Cox regression model was evaluated in order to test the statistical association between the number of metastatic sites and PFS and OS end points, and to estimate the HR; in this model, the number of metastatic sites was introduced as a continuous predictor. The same univariate model with the Mozter score added as an ordinal predictor was evaluated.
Crude survival curves were estimated using the Kaplan–Meier method; adjusted survival curves were estimated using the mean of covariates method. The prevalence of each metastatic site was entered into both multivariate Cox regression models, in order to estimate the adjusted survival functions.
All statistical tests were two sided and a p-value of <0.05 was considered statistically significant. Statistical analysis was performed using the SAS software version 9.2 (SAS Institute, NC, USA); the adjusted survival functions were estimated and plotted using STATA software version 12.1 (StataCorp, TX, USA).
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