Bevacizumab in combination with chemotherapy for the treatment of advanced ovarian cancer: a systematic review
Journal of Ovarian Research
Bevacizumab in combination with chemotherapy for the treatment of advanced ovarian cancer: a systematic review
Gerasimos Aravantinos 0
Dimitrios Pectasides 1
0 Second Department of Medical Oncology, Agioi Anargiroi Cancer Hospital , ifisia, Athens , Greece
1 Second Department of Internal Medicine, Hippokration Hospital, University of Athens School of Medicine , Athens , Greece
As increased angiogenesis has been linked with the progression of ovarian cancer, a number of anti-angiogenic agents have been investigated, or are currently in development, as potential treatment options for patients with advanced disease. Bevacizumab, a recombinant monoclonal antibody against vascular endothelial growth factor, has gained European Medicines Agency approval for the front-line treatment of advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer in combination with carboplatin and paclitaxel, and for the treatment of first recurrence of platinum-sensitive ovarian cancer in combination with carboplatin and gemcitabine. We conducted a systematic literature review to identify available efficacy and safety data for bevacizumab in ovarian cancer as well as for newer anti-angiogenic agents in development. We analyzed published data from randomized, controlled phase II/III clinical trials enrolling women with ovarian cancer to receive treatment with bevacizumab. We also reviewed available data for emerging anti-angiogenic agents currently in phase II/III development, including trebananib, aflibercept, nintedanib, cediranib, imatinib, pazopanib, sorafenib and sunitinib. Significant efficacy gains were achieved with the addition of bevacizumab to standard chemotherapy in four randomized, double-blind, phase III trials, both as front-line treatment (GOG-0218 and ICON7) and in patients with recurrent disease (OCEANS and AURELIA). The type and frequency of bevacizumab-related adverse events was as expected in these studies based on published data. Promising efficacy data have been published for a number of emerging anti-angiogenic agents in phase III development for advanced ovarian cancer. Further research is needed to identify predictive or prognostic markers of response to bevacizumab in order to optimize patient selection and treatment benefit. Data from phase III trials of newer anti-angiogenic agents in ovarian cancer are awaited.
Angiogenesis; Bevacizumab; Fallopian tube cancer; Ovarian cancer; Primary peritoneal cancer; Targeted therapies
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Introduction
Ovarian cancer is the seventh most common cancer in
women [1], with an estimated 225,500 new cases and
140,200 deaths globally in 2008 [2]. Symptoms of the
disease are non-specific, including abdominal discomfort
or fullness, dyspepsia, and bloating, which may mimic
other conditions and lead to a delay in diagnosis [1].
Consequently, 75% of women are diagnosed with
advanced disease (International Federation of Gynecology
and Obstetrics [FIGO] stage III or IV) [3], which has a
median overall survival (OS) of 1523 months and an
estimated 5-year survival of just 20% [4]. Around 90% of
all ovarian cancers are epithelial ovarian cancers (EOCs)
and are believed to arise from the ovarian surface
epithelium or mullerian derivatives, including the fallopian
tube; primary ovarian cancers also include ovarian-type
peritoneal tumors [4].
Current treatment options
Surgery is effective in most cases of early stage ovarian
cancer (FIGO stage I-IIA) with a 5-year survival rate of around
90% [5]. Adjuvant chemotherapy for well-staged early stage
ovarian cancer is controversial [4] but some studies have
shown a benefit [6]. Clinical practice guidelines developed
by ESMO recommend six cycles of single-agent carboplatin
as adjuvant treatment in patients with intermediate and
high-risk early stage ovarian cancer [4].
After surgical cytoreduction, the treatment of choice
for patients with advanced EOC (FIGO stage IIB-IIIC) is
platinum-based chemotherapy (six cycles of carboplatin
plus paclitaxel [CP] given every 3 weeks) [4]. Recently a
modified CP regimen with weekly paclitaxel resulted in
better long-term outcome than the 3-weekly regimen in
a phase III study in Japanese women with advanced
ovarian cancer [7,8], with confirmatory findings reported
in European women in the randomized, multicenter
phase III MITO-7 study [9], and in the chemotherapy
arm of the phase III GOG-0262 trial [10]. This regimen
has now been included in the NCCN treatment guidelines
[11]. Although approximately 80% of patients respond to
front-line chemotherapy, more than 70% of patients with
advanced stage disease recur within 5 years and develop
drug resistance [12,13].
For recurrent disease, the treatment choice is based on
the timing and nature of the recurrence and the extent
of prior chemotherapy [4]. Platinum-sensitive patients with
a treatment-free interval > 24 months and good
performance status should be considered for surgical
resection [4]. (...truncated)