Abagovomab

To assess the effect and toxicity of CA125-targeted antibody used as maintenance therapy for advanced epithelial ovarian cancer (EOC).

Two reviewers searched PubMed, Medline, Embase, VIP databases, and the references of selected articles for randomized controlled trials comparing maintenance CA125-targeted antibody treatment with placebo/observation. One-, two-, three-, and five-year overall survival (OS) and progression free survival (PFS) were collected. Incidence and severity of adverse events were extracted. Meta-analysis of combined risk ratio (RR) for OS , PFS, and toxicity were conducted.

Four trials including 1,259 women were identified. Meta-analysis showed the combined RR was 1.02 (95% CI, 0.85-1.22) for three-year OS and 0.98 (95% CI, 0.70-1.39) for the three-year PFS. This review found that abagovomab and oregovomab caused toxicity no more than placebo.

CA125-targeted antibody used as maintenance therapy alone is not more effective than placebo but they were safe as maintenance therapy.

CA125, the most widely used ovarian cancer biomarker, was first identified approximately 35 years ago in an antibody screen against ovarian cancer antigen. Two decades later, it was cloned and characterized to be a transmembrane mucin, MUC16. Since then, several studies have investigated its expression, functional, and mechanistic involvement in multiple cancer types. Antibody-based therapeutic approaches primarily using antibodies against the tandem repeat domains of MUC16 (e.g., oregovomab and abagovomab) have been the modus operandi for MUC16-targeted therapy, but have met with very limited success. In addition, efforts have been also made to disrupt the functional cooperation of MUC16 and its interacting partners; for example, use of a novel immunoadhesin HN125 to interfere MUC16 binding to mesothelin. Since the identification of CA125 to be MUC16, it is hypothesized to undergo proteolytic cleavage, a process that is considered to be critical in determining the kinetics of MUC16 shedding as well as generation of a cell-associated carboxyl-terminal fragment with potential oncogenic functions. In addition to our experimental demonstration of MUC16 cleavage, recent studies have demonstrated the functional importance of carboxyl terminal fragments of MUC16 in multiple tumor types. Here, we provide how our understanding of the basic biologic processes involving MUC16 influences our approach toward MUC16-targeted therapy. Cancer Res; 75(22); 4669–74. ©2015 AACR.