Post-docetaxel in Castration-Resistant Prostate Cancer
Post-docetaxel in Castration-Resistant Prostate Cancer
For each trial, the experimental treatment was compared with the control one. Overall survival (OS) was evaluated in the experimental arms over the control arms in the entire cohort, and in the patients with poor PS based on the hazard ratio (HR), and relative 95% confidence interval (CI) was reported in the study results. Patients with poor PS were defined based on ECOG scale and have the PS=2.
We reviewed PubMed for citations from January 2005 to December 2012. The search criteria were limited to articles published in English language and phase III clinical trials. The entry term for the search was 'CRPC.' The search was restricted to randomized controlled trials in which the experimental treatment was compared with the control one in CRPC patients. If more than one publication was found for the same trial, the most recent was considered for analysis. Other characteristics required for article inclusion were a previous treatment with docetaxel and the inclusion of patients with PS equal to two other than the availability of data for OS.
Study quality was assessed by using the Jadad 7-item scale that included the randomization, double-blinding and withdrawals; the score was reported between 0 and 5.
Data extraction was conducted independently by RI and AA according to the preferred reporting items for systematic review and meta-analysis statement, and any type of discrepancies was resolved by consensus. Data extracted for each trial were: first author's name, years of publication, trial phase, the number of patients evaluable, the number of patients with PS-2, the number of arms, randomization rate, drugs used in the experimental and in the control arm, dosage, median age, percentage of bone metastases, median follow-up, median treatment duration, median progression-free survival and median OS with the relative HR and 95% CI, in overall, PS-0/1 and PS-2 population.
For the calculation of the incidence of patients with PS=0–1 and PS=2, the number of patients in each group and the total number of patients enrolled in the study were extracted from the baseline characteristic of patients of the selected trials.
The HRs and the relative 95% CI for OS in the entire cohort, PS=0–1 and in PS=2 patients were extracted from each study. To calculate the 95% CIs, the variance of a log-transformed study-specific HR was derived using the delta method. Statistical heterogeneity between trials included in the meta-analysis was assessed using Cochrane's Q statistic, and inconsistency was quantified with I statistic (100% × ([Q−df)/Q]). The assumption of homogeneity was considered invalid for P-values less than 0.1. Summary HR was calculated using random- or fixed-effects models depending on the heterogeneity of included studies. When substantial heterogeneity was not observed, the pooled estimate calculated based on the fixed-effects model was reported using the inverse variance method.
When substantial heterogeneity was observed, the pooled estimate calculated based on the random-effects model was reported using the Der Simonian et al. method, which considers both within- and between-study variations. Publication bias was evaluated using to funnel plots (plots of study results against precision) and with the Begg et al. and Egger et al. tests. A two-tailed p-value of less than 0.05 was considered statistically significant. All data were collected using Microsoft Office Excel 2007; statistical analyses were performed using PASW statistic software (version 18) and RevMan software for meta-analysis (v. 5.2.3).
Materials and Methods
Definition of the Outcome
For each trial, the experimental treatment was compared with the control one. Overall survival (OS) was evaluated in the experimental arms over the control arms in the entire cohort, and in the patients with poor PS based on the hazard ratio (HR), and relative 95% confidence interval (CI) was reported in the study results. Patients with poor PS were defined based on ECOG scale and have the PS=2.
Selection of the Studies
We reviewed PubMed for citations from January 2005 to December 2012. The search criteria were limited to articles published in English language and phase III clinical trials. The entry term for the search was 'CRPC.' The search was restricted to randomized controlled trials in which the experimental treatment was compared with the control one in CRPC patients. If more than one publication was found for the same trial, the most recent was considered for analysis. Other characteristics required for article inclusion were a previous treatment with docetaxel and the inclusion of patients with PS equal to two other than the availability of data for OS.
Study quality was assessed by using the Jadad 7-item scale that included the randomization, double-blinding and withdrawals; the score was reported between 0 and 5.
Data Extraction
Data extraction was conducted independently by RI and AA according to the preferred reporting items for systematic review and meta-analysis statement, and any type of discrepancies was resolved by consensus. Data extracted for each trial were: first author's name, years of publication, trial phase, the number of patients evaluable, the number of patients with PS-2, the number of arms, randomization rate, drugs used in the experimental and in the control arm, dosage, median age, percentage of bone metastases, median follow-up, median treatment duration, median progression-free survival and median OS with the relative HR and 95% CI, in overall, PS-0/1 and PS-2 population.
Statistical Method
For the calculation of the incidence of patients with PS=0–1 and PS=2, the number of patients in each group and the total number of patients enrolled in the study were extracted from the baseline characteristic of patients of the selected trials.
The HRs and the relative 95% CI for OS in the entire cohort, PS=0–1 and in PS=2 patients were extracted from each study. To calculate the 95% CIs, the variance of a log-transformed study-specific HR was derived using the delta method. Statistical heterogeneity between trials included in the meta-analysis was assessed using Cochrane's Q statistic, and inconsistency was quantified with I statistic (100% × ([Q−df)/Q]). The assumption of homogeneity was considered invalid for P-values less than 0.1. Summary HR was calculated using random- or fixed-effects models depending on the heterogeneity of included studies. When substantial heterogeneity was not observed, the pooled estimate calculated based on the fixed-effects model was reported using the inverse variance method.
When substantial heterogeneity was observed, the pooled estimate calculated based on the random-effects model was reported using the Der Simonian et al. method, which considers both within- and between-study variations. Publication bias was evaluated using to funnel plots (plots of study results against precision) and with the Begg et al. and Egger et al. tests. A two-tailed p-value of less than 0.05 was considered statistically significant. All data were collected using Microsoft Office Excel 2007; statistical analyses were performed using PASW statistic software (version 18) and RevMan software for meta-analysis (v. 5.2.3).
