title: Pooled safety and efficacy analysis examining the effect of performance status on outcomes in nine first-line treatment trials using individual data from patients with metastatic colorectal cancer.
abstract: OBJECTIVE
  Performance status (PS) is a prognostic factor in patients with metastatic colorectal cancer. Clinical trials typically enroll less than 10% of patients with a PS of 2 (PS2); thus, the benefit of systemic chemotherapy in PS2 patients is uncertain.
  
  
  METHODS
  Individual data from 6,286 patients (509 PS2 patients) from nine clinical trials were used to compare treatment efficacy by PS. Progression-free survival (PFS), grade > or = 3 adverse events, 60-day all-cause mortality, overall survival (OS), and response rate (RR) were explored in the full set of nine trials and in the five trials comparing first-line monotherapy with combination therapy.
  
  
  RESULTS
  Compared with patients with PS of 0 or 1, PS2 patients had significantly higher rates of grade > or = 3 nausea (8.5% v 16.4%, respectively; P < .0001) and vomiting (7.6% v 11.9%, respectively; P = .006) and 60-day all-cause mortality (2.8% v 12.0%, respectively; P < .0001). PS2 was prognostic for PFS (hazard ratio [HR] = 1.52; P < .0001; median PFS, 7.6 months for PS 0 or 1 v 4.9 months for PS2), OS (HR = 2.18; P < .0001; median OS, 17.3 months for PS 0 or 1 v 8.5 months for PS2), and RR (odds ratio = 0.61; P < .0001; 43.8% for PS 0 or 1 v 32.0% for PS2). The relative benefit and toxicity of experimental versus control treatment and monotherapy versus combination therapy were not different in PS 0 or 1 patients versus PS2 patients.
  
  
  CONCLUSIONS
  In clinical trials, PS2 patients derive similar benefit from superior treatment as patients with PS of 0 to 1 but with an increased risk of toxicities and 12% 60-day mortality. Although current treatment provides benefit, new approaches are required to approach 1-year median survival for PS2 patients.
authors.affiliation: Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA. sargent.daniel@mayo.edu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.forename: Claus Henning
authors.initials: CH
authors.lastname: Köhne
authors.forename: Hanna Kelly
authors.initials: HK
authors.lastname: Sanoff
authors.forename: Brian M
authors.initials: BM
authors.lastname: Bot
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Seymour
authors.forename: Aimery
authors.initials: A
authors.lastname: de Gramont
authors.forename: Ranier
authors.initials: R
authors.lastname: Porschen
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Saltz
authors.forename: Philippe
authors.initials: P
authors.lastname: Rougier
authors.forename: Christopher
authors.initials: C
authors.lastname: Tournigand
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Stephens
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult