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LiFE re
Literature for ENYGO
Medical treatment of primary ovarian cancer
Editor Kamil Zalewski, Kristina Lindemann, Michael J. Halaska
Descriptive summary
AGO-OVAR-12, a double-blind phase III trial randomised 1366 patients
(2:1) with FIGO stage IIB-IV ovarian cancer (OC) to either to receive six
cycles of carboplatin and paclitaxel with nintedanib or placebo after
upfront debulking surgery [1]. Nintedanib inhibits the VEGF receptor,
platelet-derived growth factor receptor, and fibroblast growth factor
receptor. The addition of nintedanib significantly (p=0.024) increased
progression-free survival (PFS) from 16.6 months (95 % CI 13.9–19.1)
to 17.2 months (95 % CI 16.6–19.9). No significant differences were
noted in subgroups according to residual tumour. Quality of life was
not adversely affected during treatment with nintedanib, despite more
frequent gastrointestinal side effects on nintedanib.
Chan et al. report on a phase III trial with 692 primary OC patients ran-
domised to 6 cycles of 3 weekly paclitaxel (175 mg/m2) + carboplatin (6
AUC), or dose-dense weekly paclitaxel (80 mg/m2)/3 weekly carboplatin
(AUC, 6). Patients elected for bevacizumab or not and were prospectively
stratified for this factor [2]. Weekly paclitaxel was not associated with
longer PFS, as compared with standard treatment (14.7 vs. 14.0 months,
p=0.18) in the population as a whole. Among patients who did not re-
ceive bevacizumab, weekly paclitaxel was associated with superior PFS
(14.2 vs. 10.3 months; hazard ratio, 0.62; 95 % CI, 0.40 to 0.95; P=0.03).
Tewari et al. analysed post-hoc whether time from surgery to initiation
of chemotherapy impacts overall survival (OS) in GOG 218 [3]. For 81
patients with stage IV disease who underwent complete resection,
the risk of death increased when the time from surgery to initiation of
chemotherapy exceeded 25 days.
Bouchard-Fortier et al. retrospectively compared the toxicity and
tolerability of intraperitoneal (IP) cisplatin to IP carboplatin in 141 women confirming the low response rate compared to high-grade serous ovarian
with optimally cytoreduced OC [4]. The IP cisplatin group experienced
significantly more toxicities than those treated with IP carboplatin (grade
3 nausea and vomiting, grade 3 neuropathy and grade 2–3 neutropenia).
No difference in PFS (p = 0.602) or OS (p = 0.107) was found between
the groups. Three international randomised phase III trials (iPocc trial,
GOG 252, OV-21/GCIG) which will hopefully provide level 1 evidence as
to whether IP carboplatin is non-inferior to IP cisplatin.
The benefit of IP chemotherapy in OC has been confirmed by a Cochrane
review. IP chemotherapy increases both PFS (5 studies, 1311 women; HR
= 0.78; 95 % CI: 0.70 to 0.86) and OS (8 studies, 2026 women; HR = 0.81;
95 % confidence interval (CI): 0.72 to 0.90) [5]. The optimal indication
remains unclear.
Continued on the next page 
International Journal of Gynecological Cancer, Volume 26, Supplement #1
OVARIAN CANCER
Another Cochrane review assessed the role of adjuvant chemotherapy
(AC) in FIGO stage I-IIa OC [6]. Four studies were included and demon-
strated that adjuvant platinum-based chemotherapy prolongs survival
in women with early-stage OC (HR 0.67, 95 % CI 0.53 to 0.84; 1170
women). The survival benefits may be greatest in women with high-risk
disease, but uncertainty remains for lower-risk early-stage disease.
Decisions regarding adjuvant treatment in these patients should be
mindful of this uncertainty, consider adverse events, and take individual
factors into account.
Mahdi et al. retrospectively investigated whether patients with known
BRCA status, (gBRCA_mut +, n=30 and gBRCA_mut -, n=106), who
received platinum-based neoadjuvant chemotherapy (NAC) for FIGO
II-IV ovarian, fallopian tube, and primary peritoneal cancers, had an
improved outcome compared to patients with unknown BRCA sta-
tus (BRCA_mut_unk, n=166) [7]. There was no difference in surgical
outcome (rates of complete cytoreduction and bowel resection) between
the groups. gBRCA_mut + patients had non-significantly longer PFS
compared to gBRCA_mut_unk and gBRCA_mut − (19.1 vs. 15.1 vs. 15.7
months respectively). BRCA_mut + and BRCA_mut − patients had longer
overall survival compared to BRCA_mut_unk patients (50.5 vs. 54.1 vs.
36.5 months respectively, p = 0.009). Selection bias may explain the
favourable outcomes in BRCA_mut − patients, as patients who had good
response to chemotherapy and favourable outcome may be more likely
to undergo BRCA testing.
Grabowski et al. retrospectively analysed sensitivity to chemotherapy
in 39 patients with primary low-grade serous ovarian cancer (LGSOC)
in advanced disease stage after upfront surgery with macroscopic
residual disease (RD) (>1 cm) in the AGO megadatabase [8]. An objective
response to platinum-based chemotherapy was observed at 23.1 %,
cancer (HGSOC). Patients with complete cytoreduction had significantly
better progression free survival and overall survival compared to those
with RD after primary surgery.
Ruscito et al. discussed the current role of cediranib (a tyrosine kinase
inhibitor targeting VEGF receptors) in the treatment of OC [9]. A system-
atic review on chemotherapy in ovarian germ cell tumours (OGCT) also
summarised guidelines for the management of OGCT [10].
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