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.

Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

“…CA-125, which has been previously evaluated for this purpose, is not sufficiently predictive to be used as a primary endpoint in clinical trials. A large retrospective analysis of the CALYPSO phase III trial in relapsed HGSOC unexpectedly showed that early decline in CA-125 was more likely in the inferior arm, leading the authors to conclude that early change in CA-125 is a poor surrogate for progression-free survival [51]. More recently, alternative criteria for CA-125 response in clinical trials have been explored [52]; however, no reliable model has yet been identified for biomarker-driven trials.…”

Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients

“…Several analyses of CALYPSO have been undertaken (Gladieff et al , 2011; Joly et al , 2011; Kurtz et al , 2011; Lee et al , 2011). In the current analysis, OS of CD and CP were evaluated.…”

Circulating tumor cells as a new and additional approach to follow-up patients with serous low-grade ovarian adenocarcinoma – a case report and review of the literature

“…The levels of CA125 are higher with increasing age, use of hormone therapy, former smoking and history of breast cancer, but can be lower after hysterectomy, in current smokers, obese and non-white women [18,19]. Moreover, the capacity of determining good prognosis in early declines from baseline [20] is lost if the neoplasm doesn't express significant levels of CA125.…”