title: Randomized controlled trials in relapsed/refractory chronic lymphocytic leukemia: a systematic review and meta-analysis.
abstract: This systematic literature review with meta-analysis was conducted on the clinical efficacy and safety of interventions used in the treatment of chronic lymphocytic leukemia (CLL). We systematically searched databases (PubMed, Cochrane Library, and Embase; 1997 to August 2, 2012), conference abstracts, bibliographic reference lists, recent reviews, and Clinicaltrials.gov. Primary efficacy outcomes were objective response rate, progression-free survival, and overall survival. Safety end points were Grade 3/4 toxicities, serious adverse events, withdrawals because of toxicity, and deaths due to toxicity. Studies were selected if they were randomized controlled trials (RCTs) reporting on the efficacy or safety of relapsed or refractory CLL and if outcomes for CLL were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 6 RCTs of pharmacologic treatment for relapsed/refractory CLL. The most common drugs investigated (alone or in combination) were fludarabine and cyclophosphamide. When reported, median overall survival ranged from 27.3 to 52.9 months, and overall response rate from 58% to 82%. Although meta-analysis of efficacy results was considered, details are not presented because only 3 studies qualified and the common comparator treatment was not clinically relevant. The relatively small number of RCTs, few overlapping treatment arms, and variability in end points studied make it difficult to formally compare therapies for relapsed/refractory CLL. Significant variability in RCT features presents a further challenge to meaningful comparisons. Additional well-designed RCTs are needed to fully understand the relative efficacy and safety of older and more recently developed therapies.
authors.affiliation: RTI Health Solutions, Boston, MA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Police
authors.affiliation: Global Evidence and Value Development, Sanofi, Cambridge, MA. Electronic address: Peter.Trask@sanofi.com.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Trask
authors.affiliation: RTI Health Solutions, Research Triangle Park, NC.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Global Evidence and Value Development, Sanofi, Chilly-Mazarin, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Olivares
authors.affiliation: RTI Health Solutions, Research Triangle Park, NC.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Khan
authors.affiliation: Global Evidence and Value Development, Sanofi, Chilly-Mazarin, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Abbe
authors.affiliation: RTI Health Solutions, Research Triangle Park, NC.
authors.forename: Ann
authors.initials: A
authors.lastname: Colosia
authors.affiliation: RTI Health Solutions, Manchester, United Kingdom.
authors.forename: Annete
authors.initials: A
authors.lastname: Njue
authors.affiliation: RTI Health Solutions, Research Triangle Park, NC.
authors.forename: Beth
authors.initials: B
authors.lastname: Sherrill
authors.affiliation: Oncology Research and Development, Sanofi, Cambridge, MA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ruiz-Soto
authors.affiliation: RTI Health Solutions, Boston, MA.
authors.forename: James A
authors.initials: JA
authors.lastname: Kaye
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: Biologic therapy; Eefficacy; Safety; Treatment