PROs are significantly associated with clinically relevant time-to-event efficacy outcomes in clinical trials and may complement and help predict traditional clinical practice methods for monitoring patients for disease progression.

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Objectives: We explored the temporal relationship between PRO changes, which are used to measure therapeutic impact, and subsequent clinical outcomes in mCRPC. MethOds: COU-AA-301 was a multinational, double-blind, randomized phase 3 trial of abiraterone acetate plus prednisone compared with prednisone alone in mCRPC patients progressing after chemotherapy, with an Eastern Cooperative Oncology Group performance status of ≤ 2. Using data from COU-AA-301 (N = 1195) over the first 181 days of treatment, we explored relationships between changes in clinical time-to-event outcomes and PROs measuring fatigue, pain, physical well-being (PWB), functional well-being (FWB), and prostate cancer-specific signs and symptoms. Cox regression models were developed to assess the relationship between each PRO (separately and for all simultaneously), and overall survival (OS) and radiographic progression-free survival as dependent variables, adjusting for important baseline clinical and PRO characteristics. Results: In each individual model, patients with PRO improvements had a reduced risk of death and radiographic progression compared with patients with worsening or stable PROs during follow-up. Hazard ratios (95% confidence intervals) for OS in patients with improved fatigue intensity, pain intensity, PWB, FWB, and prostate cancer-specific symptoms were 0.

240 Background: PROs are used to measure therapeutic impact. The relationship between PROs and clinical outcomes is not well described. Methods: COU-AA-301 (301) and COU-AA-302 (302) were phase 3 trials of abiraterone acetate + prednisone (P) vs P in post-docetaxel and chemotherapy-naïve mCRPC pts, respectively. Using Cox regression models, we explored the association between self-reported fatigue, pain, physical well-being (PWB), functional well-being (FWB), and PC-specific (PCS) signs and symptoms, and OS and rPFS over the first 181 days, regardless of treatment, using data from 301 (N = 1195) and, separately, from 302 (N = 1088). Pts in 301 had more advanced disease and were more symptomatic at entry; pts in 302 were asymptomatic/mildly symptomatic. PRO improvements were assessed for 301 and worsening was assessed for 302. Results: In 301, pts with PRO improvements had reduced risk of death and radiographic progression (p < 0.0001) vs pts with worsening or stable PROs (Table). When all PROs were included in a multivariate (MV) model, all except pain intensity were significantly associated with OS; pain intensity, PWB, and FWB improvements were significantly associated with reduced radiographic progression. Pts in 302 with worsening PROs had greater risk of radiographic progression (p ≤ 0.02) vs pts with improved or stable PROs (Table). When all PRO end points were included in an MV model, worsening PWB remained significantly associated with worse rPFS. There were too few events at cutoff to explore the relationship between PROs and OS in 302. Conclusions: These results reinforce the clinical meaningfulness of self-reported symptoms and suggest that PROs can be used in combination with clinical measures in practice. Clinical trial information: NCT00887198; NCT00638690. [Table: see text]

IntroductIon: The three main novel anticoagulants (NOACs) currently licensed in Europe, apixaban, dabigatran and rivaroxaban, have all been directly compared against warfarin in randomised controlled trials. However, none of the three drugs have been directly compared against each other. Thus, there has been an increase in the number of meta-analyses and indirect comparisons published comparing the relative efficacy and safety of these novel anticoagulants against each other via warfarin as a common comparator. objectIves: Systematically review all meta-analyses and indirect comparisons evaluating the NOACs against warfarin for the prevention of stroke in patients with AF and critically appraise the statistical methods used to do so. Methods: Systematic searches of EMBASE, MedLine, EBM Reviews, EconLIT as well as manual searches of ClincalTrials. gov, the Cochrane Library, CADTH, NICE, NHSEED and HTA were conducted. Data was abstracted from any citation applying statistical methods to compare the efficacy and safety of NOACs for the prevention of AF-related stroke. Information regarding the statistical approach; model assumptions; data presentation; interpretation of the evidence; and discussions of internal and external validity was used to quality rate each study. results: Bucher's method of adjusted indirect comparison was most widely used. There were generally three main model assumptions required: the similarity, homogeneity and consistency assumptions, each being investigated with varying scrutiny in the studies reviewed. According to the quality assessment, the indirect comparison conducted by Wells and colleagues (2012) is of the highest relative quality. conclusIons: The limited number of RCTs available comparing the NOACs to standard therapy, creates considerable uncertainty surrounding the comparative efficacy and safety of these anticoagulants. In order to establish which individual NOAC is most likely to benefit a given patient population, indirect comparisons and meta-analyses are increasingly used. However, the quality of indirect comparison studies are variable and results should be interpreted with care.