Do patients with reduced or excellent performance status derive the same clinical benefit from novel systemic cancer therapies? A systematic review and meta-analysis

Background Whether patients with excellent and reduced performance status (PS) derive different net clinical benefit from novel anticancer systemic therapies on clinical trials is unclear. Materials and methods A systematic review was conducted of randomised controlled trials (RCTs) cited for drug approvals between 2006 and August 2015 by the Food and Drug Administration, the European Medicines Agency and Health Canada. Included studies had overall survival (OS) and/or progression-free survival (PFS) primary endpoints. Meta-analyses of OS/PFS based on PS dichotomised into excellent and reduced subgroups were performed using random effects. Results The systematic review identified 110 RCTs, with none reporting PS subgroup analyses for toxicity and 66 (60%) for efficacy. For these 66 RCTs involving 44 511 patients, pooled HRs for excellent and reduced groups were 0.65 (95% CI 0.61 to 0.70) and 0.67 (95% CI 0.62 to 0.72), respectively, with no difference between the two groups (p=0.68). Sensitivity analyses based on drug or cancer type and type of endpoints (OS or PFS) demonstrated similar results. Conclusions No decrease in relative efficacy from novel systemic therapy was found for patients with reduced PS when compared with patients with excellent PS for the range which were included in modern RCTs. Reporting of PS subgroup analyses of toxicities and more inclusion of patients with borderline low PS in RCTs should be considered for a more comprehensive understanding of the net clinical benefits of contemporary systemic therapies in patients across the spectrum of different PS.