title: Assessment of tumor response as a surrogate endpoint of survival in recurrent/platinum-resistant ovarian carcinoma: a Gynecologic Oncology Group study.
abstract: OBJECTIVE
  We investigated whether tumor response rate (TRR), disease control rate (DCR), or progression-free survival (PFS) was a valid surrogate for overall survival (OS) in phase II trials of second-line therapies for patients with platinum-resistant ovarian carcinoma (PROC).
  
  
  METHODS
  We retrospectively evaluated data from 11 second-line phase II trials conducted for PROC by the Gynecologic Oncology Group (GOG). TRR included complete response and partial response (CR/PR) and DCR was defined as either tumor response or stable disease (CR/PR+SD). Survival by tumor response was analyzed using a landmark approach. Correlations of OS with TRR, DCR, and PFS were estimated.
  
  
  RESULTS
  Among 407 patients analyzed the TRR was 13.8% (56/407) and DCR was 38.8% (158/407). Median OS was 10.2 months while median PFS was only 2.4 months. Median OS among patients with a best response of CR/PR, SD, and progressive disease (PD) was 13.3, 12.1 and 5.7 months, respectively, showing no difference between CR/PR and SD. From a protocol level, DCR correlated better with OS (Pearson r=0.748; Tau-b r=0.514) compared to TRR (Pearson r=0.564; Tau-b r=0.404). PFS rate at 6 months (Pearson r=0.661; Tau-b r=0.514) also correlated strongly with OS.
  
  
  CONCLUSIONS
  This study demonstrates the limitations of the use of response rate alone in PROC. Clinical benefit, as defined by OS, appeared similar for patients with an objective response and those with SD. The DCR, by including tumor response and SD may have utility as a surrogate endpoint for survival in phase II therapeutic trials in PROC.
authors.affiliation: Cleveland Clinic Foundation, Case Western Reserve University, Cleveland, OH 44195, USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Rose
authors.forename: Chunqiao
authors.initials: C
authors.lastname: Tian
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bookman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D023381:Endpoint Determination / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000379:methods; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds