Epithelial ovarian cancer is the most frequently diagnosed ovarian malignancy and the leading cause of death from gynaecological cancers. Standard therapy consists of surgery followed by chemotherapy. Although initial response rates are high, the majority of patients with advanced disease relapse. No curative treatment is available for recurrent disease. The observation that the presence of certain immune cells in tumours is associated with improved survival, suggests that stimulation of anti-tumour immune responses, i.e. immunotherapy, might be a useful approach to improve prognosis of ovarian cancer. In this review, the feasibility of antigen-specific active immunotherapy is evaluated. Antigen-specific active immunotherapy aims at the induction of tumour-directed immune responses through the administration of a tumour-antigen, a molecule that is preferentially expressed by tumour cells and can induce immune responses. As immunotherapy is a novel treatment strategy early phase studies were also included. Information on clinical and immunological responses, and adverse events was collected.
Thirty-six studies, which included 1780 ovarian cancer patients, were identified between 1966 and 2009. The most frequently described strategy (1505 patients in 15 studies) was administration of antibodies targeting CA-125. Most of these primarily evaluated safety and immunological responses. Five studies described severe flu-like and gastro-intestinal symptoms in 7 to 30% of patients. Antibodies and immune cells recognising CA-125 were frequently detected, albeit response rates varied between studies. Despite promising immunological responses, three large studies found equal survival rates for patients treated with placebo or CA-125 directed antibody. Because there is currently no high quality evidence of clinical benefit, antibody therapy targeting CA-125 should in its current form not be incorporated in standard treatment.
For strategies not relying on antibody administration, similar conclusions cannot be drawn as these have not yet been tested in large trials to evaluate clinical efficacy of treatment. These were generally small studies primarily investigating vaccine safety and immunogenicity. Overall, treatment was well-tolerated, with inflammatory side effects at injection site most frequently reported. Antibodies and immune cells were induced by most strategies studied, but their clinically efficacy still has to be evaluated in large trials.
Based on a lack of uniformity in included studies, we strongly advocate universal adoption of response definitions, guidelines for adverse events reporting, and directives for trial conduct and reporting. Furthermore, results from ongoing RCTs should be awaited and furhter RCTs should be conducted.