abagovomab fails placebo phase111 trial

Abagovomab Does Not Prolong Progression-Free Survival in Advanced Ovarian Cancer
Jenny Ko, PharmDJune 04, 2011 Print Email Reprint PermissionsText: A | A | A

RELATED CONDITIONSGynecologic cancers CHICAGO?At the American Society of Clinical Oncology's 2011 Annual Meeting, results of the MIMOSA trial, presented by Jacobus Pfisterer, MD, PhD, from Klinikum Solingen, Germany, and colleagues, demonstrated that abagovomab does not improve progression-free survival in patients with advanced ovarian cancer.

Abagovomab is a murine monoclonal anti-idiotypic antibody that has been shown to induce an active immune response against CA125, a tumor-associated antigen in advanced ovarian cancer patients. MIMOSA (Monoclonal Antibody Immunotherapy for Malignancies of the Ovary by Subcutaneous Abagovomab), a Phase 2/3 randomized, double-blind, placebo-controlled trial, evaluated the efficacy of abagovomab in patients with histological and CA125 confirmed FIGO stage 3/4 epithelial ovarian, fallopian tube, or primary peritoneal cancer after complete response to platinum-taxane first-line chemotherapy (a maximum of 12 weeks after the last cycle of therapy). The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS),immunological response, and safety.

An estimated 870 patients (with a mean follow-up of 18 months) were required to observe at least 535 recurrences, which provides a power >90% in rejecting the null hypothesis of equality between abagovomab and placebo on PFS according to a hazard ratio (HR) of 1.33, in which median placebo PFS time is 18 months, significance level 5% (two-sided), and the overall dropout rate 10%.

Patients were randomized to receive either abagovomab 2mg/mL or placebo subcutaneously every 2 weeks for 6 weeks (induction); then every 4 weeks (maintenance) until recurrence, or up to 21 months after the last patient had been randomized. Randomization was based on a prospective stratification of the following prognostic factors: FIGO stage (3/4); tumor size after debulking (residual tumor <1cm, >1cm); and CA125 serum levels after the third cycle (<35U/mL, >35U/mL). Baseline patient characteristics were balanced between the two arms. The Cox proportional hazard model was used for adjusting the primary analysis.

The MIMOSA study enrolled 888 patients, 593 in the abagovomab arm and 295 in the placebo arm. A total of 554 events were observed at the end of the double-blind observation period. Median duration of follow-up was 28.1 months and the mean number of treatment administrations was 18. The median PFS [95% CI] for abagovomab was 13.24 [10.612?13.602] months compared with 13.21 [10.612?16.000] for placebo; HR 1.099 [0.919?1.315]; P=0.301. Overall survival rates at 1 year (93% vs. 95%) and 3 years (67% vs. 68%) were comparable between the abagovomab and placebo arms, respectively.

Overall tolerability was consistent with previous studies evaluating abagovomab. Injection-site reactions were the most commonly reported adverse event (AE) occurring in both arms (78.6% vs. 74.2%). AEs that occurred more frequently in the abagovomab group compared with the placebo group were diarrhea (8.8% vs. 4.7%), abdominal pain (7.6% vs. 4.4%), and fatigue (20.7% vs. 15.9%).

Dr. Pfisterer concluded that abagovomab maintenance treatment after debulking surgery and successful platinum and taxane first-line chemotherapy did not prolong progression-free survival in advanced ovarian cancer patients.

http://www.empr.com/abagovomab-does-not-prolong-progression-free-survival-in-advanced-ovarian-cancer/article/204503/