title: Early decline in cancer antigen 125 as a surrogate for progression-free survival in recurrent ovarian cancer.
abstract: We used data from 886 patients from the CAELYX in Platinum Sensitive Ovarian Patients (CALYPSO) trial, recruited between April 2005 and September 2007, to examine the role of early decline in cancer antigen 125 (CA125) and early tumor response as prognostic factors and surrogates for superiority of treatment with carboplatin-pegylated liposomal doxorubicin (CPLD) compared with carboplatin-paclitaxel (CP) in a landmark analysis. Progression-free survival (PFS) was estimated by Kaplan-Meier analyses. We used univariate and multivariable Cox proportional hazards analyses to assess early decline and early response as surrogates for CPLD treatment benefit compared with CP. All statistical tests were two-sided. Early decline (defined as rate of CA125 decrease of at least 50% per month) was associated with improved PFS (adjusted hazard ratio [HR] for progression = 0.81, 95% confidence interval [CI] = 0.67 to 0.97, P = .02) but early response (complete or partial responses) was not. CPLD was associated with improved PFS compared with CP (HR = 0.82, 95% CI = 0.69 to 0.96, P = .01). However, fewer CPLD patients had an early decline (161 [37.4%] vs 233 [51.2%], P < .001) or an early response (146 [33.9%] vs 176 [38.7%], P = .14) compared with CP patients. The PFS for CPLD patients did not change statistically significantly after adjustment for early decline (adjusted HR = 0.80, 95% CI = 0.68 to 0.94, P = .007). These findings are opposite to what would be expected if these markers were good surrogates for treatment benefit.
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Locked Bag 77, Camperdown, Sydney, NSW 1450, Australia. chee.lee@ctc.usyd.edu.au
authors.forename: Chee K
authors.initials: CK
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Friedlander
authors.forename: Chris
authors.initials: C
authors.lastname: Brown
authors.forename: Val J
authors.initials: VJ
authors.lastname: Gebski
authors.forename: Alexander
authors.initials: A
authors.lastname: Georgoulopoulos
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Donadello
authors.forename: Barbara
authors.initials: B
authors.lastname: Schmalfeldt
authors.forename: Rémy
authors.initials: R
authors.lastname: Delva
authors.forename: Mansoor Raza
authors.initials: MR
authors.lastname: Mirza
authors.forename: Philippe
authors.initials: P
authors.lastname: Sauthier
authors.forename: Eric
authors.initials: E
authors.lastname: Pujade-Lauraine
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lord
authors.forename: R John
authors.initials: RJ
authors.lastname: Simes
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D016190:Carboplatin / Q000008:administration & dosage; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel