" " Information on adverse events was
frequently limited."
PLAIN LANGUAGE SUMMARY:
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 (new) 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.
ABSTRACT:
Objectives
To assess feasibility of antigen-specific active immunotherapy for ovarian cancer. Primary outcomes are clinical efficacy
and antigen-specific immunogenicity with carrier-specific immunogenicity and side-effects as secondary outcomes.
