A randomized trial in ovarian cancer (OC) of early treatment of relapse based on CA125 level alone versus delayed treatment based on conventional clinical indicators (MRC OV05/EORTC 55955 trials).

1 Background: Serum CA125 often rises several months before women with OC have symptoms or clinical signs of relapse. OV05/55955 was designed to determine whether there were benefits from early treatment based on a confirmed elevation of CA125 levels versus delaying treatment until clinically indicated. METHODS Women with OC in clinical complete remission after first-line platinum-based chemotherapy and a normal CA125 were registered. CA125 was measured every 3 months but patients and investigators were blinded to the results, which were only monitored by the trials units. If CA125 levels exceeded twice the upper limit of normal, patients were randomized to either immediate treatment or to remain having blinded CA125 measurements with treatment commencing when clinical or symptomatic recurrence appeared. Patients in both arms were treated according to standard local practice. The primary outcome measure was overall survival. The study was designed to detect a 10% improvement in 2-year overall survival in the immediate treatment arm with at least 85% power and 5% significance level (2-sided). RESULTS 1,442 patients were registered from 59 sites in 10 countries between 1996 and 2005. Randomization closed on March 31, 2008 with 527 patients (264 immediate and 263 delayed) randomized and when the targeted number of events (deaths) were reached. 915 patients have not been randomized due to: no CA125 rise and no relapse (48%); relapse with or without CA125 rise (30%); death (6%); patient withdrawal (14%); or other reasons (2%). For randomized patients baseline characteristics were well balanced between the groups. Median age at registration was 61 years; 81% were FIGO stage III/IV. Second-line chemotherapy started a median of 5 months earlier in the immediate arm. With a median follow-up of 49 months from randomization and a total of 351 deaths, there was no evidence of a difference in overall survival between the immediate and delayed arms, hazard ratio 1.01, 95% CI 0.82-1.25, p = 0.91. CONCLUSIONS There is no survival benefit from early treatment based on a raised serum marker level alone, and therefore no value in the routine measurement of CA125 in the follow-up of ovarian cancer patients. No significant financial relationships to disclose.