title: Surrogate endpoints in second-line treatment for mCRC: a systematic literature-based analysis from 23 randomised trials.
abstract: OBJECTIVE
  To evaluate progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) as potential surrogate endpoints (SEP) for overall survival (OS) in second-line treatment for metastatic colorectal cancer (mCRC).
  
  
  METHODS
  A systematic literature search of randomised trials of second-line chemotherapy for mCRC reported from January 2000 to July 2013 was performed. Correlation coefficients weighted by number of patients in the treatment arms between median PFS, ORR and DCR with median OS were estimated.
  
  
  RESULTS
  Twenty-three trials reflecting 10 800 patients met the inclusion criteria. Median PFS and OS across all trials were 4.5 months and 11.5 months and median ORR and DCR were 11.4% and 65%, respectively. PFS showed moderate correlation with OS [RPFS = 0.73; 95% confidence interval (CI) 0.61-0.82]. In contrast, ORR only weakly correlated with OS (RORR = 0.58; 95% CI 0.38-0.72, n = 22). Despite a small number of studies (n = 10) reporting on DCR, moderate correlation with OS was observed (RDCR = 0.74; 95% CI 0.56-0.86).
  
  
  CONCLUSIONS
  Based on the available trial-level data, PFS may serve as an appropriate SEP in second-line chemotherapy for mCRC. A small number of studies revealed moderate correlation of DCR with OS that justifies further investigation.
authors.affiliation: Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich , Munich , Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Giessen
authors.forename: Ruediger Paul
authors.initials: RP
authors.lastname: Laubender
authors.forename: Donna Pauler
authors.initials: DP
authors.lastname: Ankerst
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stintzing
authors.forename: Dominik Paul
authors.initials: DP
authors.lastname: Modest
authors.forename: Christoph
authors.initials: C
authors.lastname: Schulz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mansmann
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D016001:Confidence Intervals; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D018401:Sample Size; D013997:Time Factors
chemical_list: D015415:Biomarkers