Meta-analytical methods for estimating outcomes from overall response rate in patients with relapsed/refractory...

Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is highly heterogeneous and current trials are investigating new approaches to improve outcomes. Limited data on response endpoints can confound estimation of a treatment effect when designing studies of novel agents in this setting, which can hinder study sample size calculations, especially if a net estimate is required for a 'physician's choice' comparator arm. Here we estimate complete response rate (CRR), overall response rate (ORR), and extrapolate durable response rates (DRR; CR/partial response lasting ≥16 weeks) for such a comparator arm from published ORRs in DLBCL. CRR, ORR, and DRR (if reported) were obtained from published clinical trials for approved single-agent therapies in patients with relapsed/refractory aggressive non-Hodgkin lymphoma after ≥2 prior therapies. Meta-analyses were performed to estimate CRR, ORR, and DRR based on ORR data reported from these studies. Published data from studies of eight monotherapies were included. Meta-analyses using fixed and random effects models showed a pooled estimate for a CRR of 12% (95% confidence interval [CI]: 9-15) and 11% (95% CI: 8-15), respectively, an ORR of 30% (95% CI: 25-35) and 30% (95% CI: 24-36), respectively, and a DRR of 14% (95% CI: 11-18; same for fixed and random effects models). Bayesian meta-analysis estimated a pooled DRR of 14% (95% credible interval: 11-19). CRR estimates for a physician's choice comparator arm in patients with relapsed/refractory DLBCL were 11-12%; DRR estimates were 14% regardless of methodology. Lack of consistency in reported data and choice of endpoints can be addressed using meta-analytic approaches.