Annals of Oncology 28 (Supplement 8): viii51–viii56, 2017

doi:10.1093/annonc/mdx441

SYMPOSIUM ARTICLE

Treatment of recurrent ovarian cancer

S. Pignata1*, S. C. Cecere1, A. Du Bois2, P. Harter2 & F. Heitz2

1
Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale,” Naples, Italy; 2Department
of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany

*Correspondence to: Dr Sandro Pignata, Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale,”
Via Mariano Semmola, 80131 Naples, Italy. Tel: þ39-0815903637; Fax: þ39-0815903861; E-mail: s.pignata@istitutotumori.na.it

Despite optimal surgery and appropriate first-line chemotherapy, 70%–80% of patients with epithelial ovarian cancer will
develop disease relapse. The same modalities as used primarily are available for treatment of recurrent ovarian cancer (ROC). The
rationale for repetitive surgery in ROC was based on a stable body of retrospective data; however, prospective data were
missing. Now, preliminary data from the prospective AGO-DESKTOP III give evidence that surgery for ROC seems to be of
benefit for selected patients with platinum-sensitive relapse undergoing complete resection. With respect to systemic therapy,
tumor histology, BRCA status, the platinum-free interval (PFI) and previous treatment with bevacizumab (anti-VEGF monoclonal
antibody) are considered the most important features that influence treatment choice in ROC. In patients with resistant or
refractory relapse (PFI < 6 months), monotherapy with a non-platinum drug or participation in clinical trials is indicated. The
association of non-platinum monotherapy with bevacizumab, followed by maintenance has been approved in this setting in
some European countries due to PFS benefit. In patients with partially sensitive relapse (PFI between 6 and 12 months), two
options are available: platinum doublets or non-platinum therapy (single agent or combination). The pegylated liposomal
doxorubicin/trabectedin combination represents a viable alternative in patients that cannot receive platinum. In platinum-
sensitive patients, treatment with platinum-based combinations is associated with PFS advantage compared with single agents
or non-platinum combinations. The presence of germline or somatic BRCA mutations allows platinum-responsive patients to
optimize chemotherapy efficacy and prolonging PFS by the use of olaparib (PARP inhibitor) given as maintenance therapy until
progression. In patients not pretreated with bevacizumab in first line, the carboplatin/gemcitabine/bevacizumab combination,
followed by maintenance is a viable alternative in platinum-sensitive patients (PFI> 6 months). The integration of surgery, with a
‘personalized’ approach by the use of antiangiogenic agent and of PARP inhibitors is affecting survival of patients with recurrent
disease and will help epithelial ovarian cancer to become a chronic disease.
Key words: ovarian cancer, recurrent, chemotherapy

Introduction remains—so far—an option for individual patients who should

Epithelial ovarian cancer (EOC) is an aggressive malignancy and
it is most frequently diagnosed in an advanced disease stage [1].
The mainstay of primary treatment is surgery with the goal of
complete resection [2]. Even if no complete resection is feasible
to obtain, patients still have some benefit of surgery, if tumor
reduction to residual disease <1 cm is achieved [3]. The intro-
duction of bevacizumab to the standard chemotherapy with plat-
inum/taxane and maintenance therapy up to 15 months have
improved PFS [4, 5]. Despite that, 23% of patients relapse dur-
ing or within 6 months after end of primary chemotherapy and
60% relapse after 6 months [3]. The standard approach for treat-
ing recurrent ovarian cancer (ROC) is chemotherapy and surgery
be carefully selected.
Surgery for relapsed ovarian cancer
Most recently, one of the two prospective randomized trials
designed to evaluate the impact of surgery for recurrent OC has
reported first results of an interim analysis. In this trial (DESKTOP
III), patients were recruited who had a so-called platinum-sensitive
ROC and a positive AGO (Arbeitsgemeinschaft Gynäkologische
Onkologie) Score; 408 patients with platinum-sensitive ROC
and a positive AGO score (see below) were randomized to surgery
followed by chemotherapy, or chemotherapy alone. Patients

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 Symposium article
Table 1. Overview of published series evaluating the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO)-DESKTOP Score
AGO score positive
Pts. Complete
resection (%)
Harter et al. DESKTOP II [18] 129 76.0
Harter et al. [19] 112 89.3
Janco et al. [21] 102 84.3
van de Laar et al. [22] 111 82.0
Laas et al. [23] 33 81.8
Muallem et al. [20] 139 67.0
n.a., not reported.
undergoing surgery showed a prolonged PFS compared with
patients undergoing chemotherapy alone [19.6 versus
14.0 months, hazard ratio (HR) 0.66 with 95% CI 0.52–0.83;
P < 0.001]. Subgroup analysis demonstrated that only patients
with complete resection had a benefit of surgery. Surgery was safe
as 30-, 60- and 90-day mortality was not increased in patients
undergoing surgery [6].
The rationale for conducting AGO-OVAR DESKTOP III was
based on a broad body of retrospective data. A comprehensive
review of all published retrospective series to this topic was pub-
lished in 2005 [7]. This review was limited to series with >100
patients and cytoreductive surgery for platinum-sensitive ROC,
as most of the identified series were rather small or had mixed
patient cohorts. Eight series could be identified which reported
prognostic factors for survival after cytoreductive surgery in ROC
[8–15]. Primary FIGO-stage, localization and outcome of pri-
mary surgery were never reported to be of prognostic significance
in the recurrent disease setting. Two series identified preoperative
chemotherapy as a negative prognostic factor. All series reported
surgical outcome as independent prognostic factor for survival.
The multicenter Descriptive Evaluation of preoperative Selection
KriTeria for OPerability in recurrent OVARian cancer I
(DESKTOP I OVAR) by the AGO Study Group reported only
complete resection as beneficial with an OS of 45.2 months.
There were no differences between minimal residuals of 1–10 or
>10 mm (19.7 versus 19.6 months). There were two series
describing a benefit of cytoreduction to 1–20 mm compared with
>20 mm [13] and 0.1–10 mm compared with >10 mm [14].
However, very heterogeneous patients’ cohorts and missing addi-
tional chemotherapy after surgery in a substantial frequency of
patients, limited the value of these analyses. In contrast, the larg-
est single center series published by Sehouli et al. [15] confirmed
the findings that only complete resection is beneficial. Moreover,
a large international collaborative multicenter analysis including
1100 patients showed that complete resection was strongly asso-
ciated with the improvement of survival, with a median survival
of 57.7 months, compared with 27.0 months in those patients
with residual disease of 0.1–1 cm and 15.6 months in those with
residual disease of >1 cm, respectively (P < 0.0001) [16]. In addi-
tion to complete resection, which was the strongest prognostic
factor for further survival (HR: 2.94), the DESKTOP I series
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Annals of Oncology
AGO score negative
Median OS Pts. Complete Median OS
(months) resection (%) (months)
n.a. 63 63.5 n.a.
57.3 105 66.7 33.5
n.a. 90 64.4 n.a.
n.a. 162 68.5 n.a.
n.a. 32 65.6 n.a.
54.0 70 48.5 21.7
identified absence of ascites (HR: 2.30) and postoperative
platinum-based chemotherapy (HR: 1.82) as further prognostic
factors.
In the past, it was difficult to identify suitable patients in whom
complete resection was feasible. Therefore, the reported rates of
complete resection varied between 20% and 80% [17]. The
AGO DESKTOP I study evaluated three predictive factors for
complete resection: Good performance status (ECOG 0), com-
plete resection at first surgery (alternatively, FIGO I/II in patients
with unknown residual disease after primary surgery), and
absence of ascites. Patients, in whom all these factors were
present, a complete resection was feasible in 79% (AGO-score
positive). In the subsequent AGO DESKTOP II study, this score
was validated prospectively. The study was planned to show that
a positive AGO score reaches a positive predictive value for com-
plete resection of > 66% (2 of 3 pts) with 95% probability at a sig-
nificance level of P< 0.05. Five hundred sixteen patients with
platinum-sensitive relapse were screened within 19 months.
About 32% of the patients with first relapse were operated on.
One hundred twenty-nine patients had a positive score. In
patients with a positive score, a complete resection could be
achieved in 76%, resulting in a positive validation of the AGO
score [18]. Since the publication of the DEKTOP II study, the
AGO score has been validated by several other groups [19–20]
(Table 1). Complete resection rates in patients with positive AGO
score ranged between 67.0% and 89.3%, indicating that the AGO
score is able to predict operability with complete resection with
high reliability. On the other hand, the AGO score was not
intended to give any information about inoperability. DESKTOP
II already reported complete resection rates of 63.5% in AGO-
score negative patients and in the consecutive analyses by other
groups revealed complete resection rates ranging between 48.5%
and 68.5%.
Primary surgery for advanced EOC bears a curative opportunity
for affected patients. Therefore, it seems to be appropriate to
accept an increased morbidity and even low rates of mortality. Due
to the fact, that the impact of surgery on survival of r ROC is still
not validated prospectively, and that the current understanding of
treatment of ROC is merely prolongation of survival and not cure,
morbidity and mortality are of highest importance. Perioperative
complications have been prospectively documented in DESKTOP
Volume 28 | Supplement 8 | November 2017
 Annals of Oncology
II. About 44% of patients had to receive packed blood cells, and
33% of patients had at least one perioperative complication. About
24% of patients received antibiotic treatment and 11% did
undergo relaparotomy. In a meta-analysis, the weighted mean
morbidity rate was 19.2% [24]. The 30-day mortality in
DESKTOP II was reported to be 0.8% [18], in meta-analysis 1.2%
[24] and up to 7.8% in single institutions [15].
As described earlier, the AGO DESKTOP III trial
(NCT01166737) has only presented PFS, but data on OS are still
premature. Another ongoing study investigating the role of cytore-
ductive surgery for platinum-sensitive ROC is carried out by the
Gynecologic Oncology Group (GOG) (GOG 213; NCT00565851).
Medical treatment of relapsed ovarian
cancer
Waiting for clarifications about the role of surgery in the relapsed
disease setting, actually the standard treatment is still represented
by systemic therapy.
Despite optimal surgery and appropriate first-line chemother-
apy, 80% of patients with EOC will develop a recurrence at dif-
ferent time points. The likelihood of relapse depends on many
factors, including distribution of disease at initial presentation,
success of initial surgical cytoreduction (i.e. the presence of any
residual disease), rapidity of CA125 resolution, and treatment
response after primary therapy. ROC can be detected biochemi-
cally (rising of CA125), clinically or radiologically. Subsequent
sequential treatment strategies maximize quality and length of
life but are not curative. Retreatment with chemotherapy should
not be routinely started in asymptomatic patients with CA125
progression alone. Literature data have demonstrated that early
initiation of chemotherapy is not associated to any survival
advantage and in fact will have a negative effect on quality of life
(QoL). Prognosis at relapse is mainly dominated by chemosensi-
tivity of the tumor. The choice of second-line chemotherapy
depends on several factors such as platinum-free interval (PFI),
persistent side-effects after prior treatments, schedules and toxic-
ity profiles of next therapies and patient preferences.
Until now, the PFI has been considered as the main prognostic
factor that guides the treatment choice at time of the recurrence.
The fourth International Ovarian Cancer Consensus Meeting
held in Vancouver in June 2010 on behalf of Gynecologic Cancer
InterGroup (GCIG) established definition of PFI as the interval
from the last date of platinum dose until progressive disease is
documented [25]. According to this definition, ROC has been
characterized into four different categories known as platinum-
refractory, resistant, partially sensitive, and fully sensitive
depending on when the relapse occurs after the last platinum
treatment (during treatment or within 4 weeks; between 6 and
12 months; or beyond 12 months, respectively). Although these
definitions have been used to identify different populations, the
resistance to platinum-based treatment is not a categorical varia-
ble. Furthermore, considering the recent introduction of mainte-
nance therapies, the concept of PFI has been recently challenged.
In the last consensus (5th Ovarian Carcinoma Consensus
Conference) conference of Tokyo [26], the PFI paradigm has
been partially revisited and the concept of treatment-free interval
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introduced, considering PFI, previous bevacizumab, BRCA status
and different histological subtypes.
Treatment of early relapse
Patients relapsing during first-line treatment (refractory) or in
the few following months thereafter (resistant) represent a very
heterogeneous group with various biological tumor behaviors.
This condition is linked to unfavorable prognosis, so the main
objective of treatment is to palliate symptoms and preserve QoL.
Monotherapy with non-platinum compounds has showed to be
equally effective and less toxic compared with combinations. A
Cochrane systematic review of trials in platinum-resistant EOC
found that paclitaxel, pegylated liposomal doxorubicin (PLD)
and topotecan offer similar objective response rates (10%–20%),
median PFS (3–4 months), and overall survival (12 months)
with different toxicity profiles [27]. Regarding molecular targeted
therapy, interesting data have been obtained in this setting with
antiangiogenic compounds. In the randomized phase III
AURELIA trial [28], bevacizumab in combination with standard
chemotherapy (PLD, weekly paclitaxel, or topotecan) and as sin-
gle agent maintenance until progression demonstrated to pro-
long PFS (6.7 versus 3.4 months HR 0.48; 95% CI 0.38–0.60;
P < 0.001). However, overall survival was not found prolonged,
most probably partially due to the fact patients in the standard
chemotherapy alone arm could receive bevacizumab at time of
progression [HR 0.85 (95% CI 0.85–1.08); P ¼ 0.174; median
16.6 months with bevacizumab plus chemotherapy versus
13.3 months with chemotherapy alone]. However, in a sub-group
analysis, a significant OS benefit was shown for bevacizumab in
the weekly paclitaxel group (median 22 versus 13 months).
According to those results, bevacizumab was licensed in this
setting.
Treatment of relapse after 6 months
This subgroup refers to a wide heterogeneous group that include
platinum-sensitive (PFI  12 months) and partially sensitive
(PFI  6 <12 months) patients. Chemosensitivity to platinum
compounds is supposed to increase with longer interval from the
initial therapy. For patients with PFI >12 months, the use of
platinum-based combinations (carboplatin/PLD; carboplatin/
paclitaxel and carboplatin/gemcitabine) is associated to a better
outcome (PFS, OS, ORR) compared with non-platinum or
platinum single agent treatments [29, 30]. In patients with a PFI
between 6 and 12 months (partially platinum-sensitive), two
options are available: platinum doublets or non-platinum ther-
apy (single agent or combination). The hypothesis that a benefit
could be derived from the artificial extension of PFI by introduc-
ing a non-platinum therapy in partially sensitive disease to make
the following platinum more effective has been proposed many
years ago, without any prospective confirmation of its validity.
Some studies have been designed to test this hypothesis (MITO8,
INOVATYON). The MITO 8 study a phase III trial comparing
the experimental sequence of a non-platinum single agent chemo
(NPBC) followed by a platinum based chemotherapy (PBC) ver-
sus the reversed sequence, recently demonstrated that the use of
doi:10.1093/annonc/mdx441 | viii53
 Symposium article
NPBC to artificially prolong the PFI is not effective in partially
sensitive d ROC patients [median OS was 21.8 versus
24.5 months (HR 1.38, 95% CI: 0.99–1.94, P ¼ 0.06)] [31]. This
evidence confirms that platinum-based treatment should be the
first choice in this population. A non-platinum containing dou-
blet (trabectedin plus PLD) has been recently introduced in the
treatment of patients with platinum-sensitive ROC that are not
candidate for platinum. This approach is based on the PFS
advantage observed with the combination versus PLD alone in
the OVA-301 randomized trial (median PFS of 7.4 months in the
trabectedin/PLD arm versus 5.5 months in the PLD arm) [32]. A
subgroup analysis of this trial has suggested an OS prolongation
in the same population of the MITO 8 trial, with a significant
41% decrease in the risk of death compared with PLD alone
(HR ¼ 0.59; 95% CI, 0.43–0.82; P ¼ 0.0015). Median OS was
23.0 months in the trabectedin/PLD arm versus 17.1 months in
the PLD arm. Interestingly, it has been suggested that the combi-
nation of trabectedin/PLD is able to prolong OS affecting the effi-
cacy of platinum received later after progression. This hypothesis
is under evaluation in the prospective phase III trial comparing
trabectedin/PLD, followed by platinum versus platinum-based
chemotherapy (INOVATYON trial) (ClinicalTrials.gov identi-
fier: NCT01379989). For women who are unable to tolerate plati-
num chemotherapy because of hypersensitivity, comorbidity, or
other previous toxicity, single-agent chemotherapy may be used.
Treatment of platinum sensitive relapsed OC has changed in
the last years also due to the introduction of two biological
agents: bevacizumab, a humanized monoclonal antibody target-
ing vascular endothelial growth factor, and olaparib, an inhibitor
of poly [adenosine diphosphate (ADP)-ribose] polymerase
(PARPi). Bevacizumab in combination with chemotherapy for
platinum-sensitive ROC has been approved on the basis of results
from two randomized, controlled phase III studies, GOG-0213
and OCEANS. The GOG-0213 study demonstrated that adding
bevacizumab to platinum based chemotherapy showed a non-
statistically significant OS difference of 5 months compared with
chemotherapy alone (median OS: 42.6 versus 37.3 months;
HR ¼ 0.84, 95% CI: 0.69–1.01) and a statistically significant
advantage of 3.4 months in median PFS (13.8 versus 10.4 months;
HR ¼ 0.61, 95% CI: 0.51–0.72) [33]. In the OCEANS trial, 484
women with platinum-sensitive t ROC were randomized to car-
boplatin and gemcitabine plus either bevacizumab or placebo.
The bevacizumab-containing combination was associated with a
better objective response rate (ORR, 78.5% versus 57.4% with the
non-bevacizumab containing combination), and a longer PFS
(12.4 versus 8.4 months; HR¼ 0.484; 95% CI, 0.388–0.605; log-
rank P < 0.0001). No difference in OS has been observed, prob-
ably due to crossover (HR ¼ 0.95, 95% CI: 0.77–1.17) [34].
Olaparib is the first-in-class PARP inhibitors to be licensed for
the treatment of ROC harboring deleterious BRCA mutations.
The activity of olaparib as maintenance after response to a
platinum-based chemotherapy in the platinum-sensitive high-
grade serous ROC has firstly been shown in the ‘study 19’ trial
and then confirmed in the SOLO-2 phase III trial. Maintenance
therapy with olaparib showed a 70% reduction in the risk of
progression or death compared with placebo assessed both
by investigator (median 19.1 versus 5.5 months; HR¼ 0.30, 95%
CI 0.22–0.41; P < 0.0001) and by blinded independent central
review (BICR) (median 30.2 versus 5.5 months; HR 0.25,
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0.18–0.35; P < 0.0001), and significantly longer time to second
progression (PFS2) (HR 0.50, 0.34–0.72; P ¼ 0.0002) [35, 36].
Olaparib is actually approved as maintenance after platinum
response in ROC patients with a somatic or germline BRCA
mutation.
Two other PARP inhibitors have been recently been approved
by the FDA for the treatment of recurrent disease, not only in
BRCA mutated or in platinum sensitive relapsed cases.
Niraparib, an oral highly selective, potent PARP-1 and PARP-2
inhibitor, is approved in USA for the maintenance treatment of
adult women with recurrent epithelial ovarian, fallopian tube or
primary peritoneal cancer responding to last platinum-based
chemotherapy. It is also under regulatory review in the EU for use
as maintenance treatment in patients with platinum-sensitive
ROC who are in response to platinum-based chemotherapy
based on the results of the phase III trial, the ENGOT-OV16/
NOVA study. This is an international phase III, double-blind,
placebo-controlled study that enrolled 553 patients with ROC
who had achieved either a partial or complete response (PR or
CR) to their most recent platinum-based chemotherapy. Patients
were categorized according to the presence or absence of a germ-
line BRCA mutation (gBRCA cohort and non-gBRCA cohort)
and the homologous recombination deficiency (HRD) status and
were randomly assigned in a 2 : 1 ratio to receive niraparib
(300 mg) or placebo once daily. The primary end point was PFS.
Patients in the niraparib group had a significantly longer median
PFS than those in the placebo group, i.e. 21.0 versus 5.5 months
in the gBRCA cohort (HR¼ 0.27; 95% CI, 0.17–0.41), 12.9 versus
3.8 months in the non-gBRCA cohort for patients who had
tumors with HRD (HR ¼0.38; 95% CI, 0.24–0.59) and 9.3 versus
3.9 months in the overall non-gBRCA cohort (HR¼ 0.45; 95%
CI, 0.34–0.61; P < 0.001 for all three comparisons). The results of
several secondary end points from this trial, including
chemotherapy-free interval, time to second subsequent therapy
(TSST), and PFS-2, demonstrate the positive and durable treat-
ment effect of niraparib in a broad population of patients with
ROC, regardless of the presence or absence of germline BRCA
mutations and HRD status [37].
Another PARP inhibitor, rucaparib an oral, small molecule
that targets the PARP enzyme, will probably enrich the therapeu-
tic armamentarium of BRCA-mutated EOC patients. Rucaparib
has been recently approved by the FDA as monotherapy for the
treatment of ROC patients who are carriers of deleterious (germ-
line and/or somatic) BRCA mutations [38]. The approval of ruca-
parib is based on results from two single-arm clinical trials
involving 106 women with ROC who had been treated with two
or more chemotherapy regimens and had their BRCA-mutations
confirmed by the companion diagnostic test. In the trials, known
as Study 10 and ARIEL2 (Assessment of Rucaparib In Ovarian
CancEr TriaL2) Parts 1, the drug obtained an overall response
rate of 54% (complete, 9%; partial, 45%) and a median duration
of response of 9.2 months. In the ARIEL2 Part 1, patients with
platinum-sensitive, high-grade ROC were classified into one of
three predefined HRD subgroups on the basis of tumor muta-
tional analysis: BRCA mutant (deleterious germline or somatic),
BRCA wild-type and loss of heterozygosis high (LOH high
group), or BRCA wild-type and LOH low group and treated with
oral rucaparib at 600 mg twice daily for continuous 28-day cycles
until disease progression or any other reason for discontinuation.
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 Annals of Oncology
The primary end point was PFSl. Median PFS after rucaparib
treatment was 12.8 months (95% CI 9.0–14.7) in the BRCA
mutant subgroup, 5.7 months (5.3–7.6) in the LOH high sub-
group, and 5.2 months (3.6–5.5) in the LOH low subgroup. PFS
was significantly longer in the BRCA mutant (HR¼ 0.27, 95% CI
0.16–0.44, P < 0.0001) and LOH high (HR ¼ 0.62, 95% CI 0.42–
0.90, P ¼ 0.011) subgroups compared with the LOH low sub-
group. These results confirm the potential usefulness of PARP
inhibitors in the treatment setting beyond BRCA mutation [39].
More data on rucaparib will eventually come from other trials
(ARIEL 3; ARIEL 4) exploring the role of the drug as maintenance
after chemotherapy or as single agent (https://clinicaltrials.gov/
ct2/show/NCT01968213, https://clinicaltrials.gov/ct2/show/NC
T02855944).
Chemotherapy according to tumor biology
and BRCA status: treatment in the following
lines
It is well recognized that there are five different histological types
of OC with a different genomic landscape, natural histories and
patterns of response to therapy. The existing treatment strategies
based on PFI in ROC has been largely driven by the activity of
chemotherapy found in high-grade serous (HGSOC) and endo-
metrioid (HGSEC) histology. In rare subtypes, where chemother-
apy is less effective, the option of a clinical trial with targeted
therapy may be appropriate. Several studies have been conducted
to test the activity of MEK inhibitors in low grade serous ovarian
cancer (LGSOC) [40]. The results of such studies are waited in
the near future; these drugs are associated with 15%–20%
response rate compared with 5% of chemotherapy [40].
Interesting data of hormonotherapy have also been reported in
LGSOC, during the 2016 ASCO Annual Meeting. A long-term
retrospective study of 204 patients with FIGO stage II–IV low-
grade serous carcinoma demonstrated that hormonal therapy
given as maintenance following primary treatment reduced the
risk of disease progression by 77%, compared with surveillance
(P < 0.001). Hormonal maintenance therapy was associated with
a statistically significant increase of the median PFS (64.9 versus
27.3 months; HR ¼ 0.23; P < 0.001) compared with the surveil-
lance; this benefit seems to be greater in patients without evidence
of disease after chemotherapy (median PFS 81.1 versus
29.9 months P < 0.001) and gained also a prolongation of median
overall survival (191.3 versus 106.8 months; P ¼ 0.04) [41]. In the
5th Ovarian Carcinoma Consensus Conference, the need of trials
in rare histologic subtypes, that have different prognosis and bio-
logical behavior, has been underlined and includes, among
others, clear cell cancer and mucinous tumors, that are less
responsive to standard chemotherapy options [42]. The tailored
therapy approach based on the different subtypes and tumor
biology is still far away from utilization in clinical practice.
However, there are some examples of a biology driven
approaches that can be proposed. As an example, chemotherapy
choice can be adapted according to BRCA mutation. Three stud-
ies (of which two retrospective) have shown a higher efficacy of
PLD in BRCA-mutated tumors compared with unselected cases
(RR of 7%–25%, probably due to the mechanism of action of this
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drug (DNA adducts, topoisomerse II inhibition in HRD cells,
immunomodulatory effects). In addition, trabectedin (a minor
groove DNA binder derived from marine organisms) has been
associated with high response rates and prolonged PFS when
used both as a single agent and in combination with PLD [32, 43,
44] in BRCA-mutated patients. There is no conclusive evidence
about an impact of BRCA mutations on response to taxanes (e.g.
paclitaxel). Despite the absence of prospective clinical trials, plat-
inum, PLD and trabectedin, can be considered the chemotherapy
agents of choice in the BRCA-mutated patients.
In conclusion, the treatment approach to patients with ROC
has evolved dramatically in recent years. The integration of sur-
gery, with a ‘personalized’ approach in using antiangiogenic
agents and PARP inhibitors has increased the survival of such
patients and will help EOC to become a chronic disease.
Funding
SP is recipient of a grant from AIRC (Associazione Italiana
Ricerca sul Cancro) (no grant number applies).
The publication of this supplement and the symposium on
which it is based have been supported through partnership
between the Spanish Ovarian Cancer Research Group (GEICO)
and the European Society for Medical Oncology (ESMO).
Disclosure
FH received honoraria from Roche, AstraZeneca and
PharmaMar and he received travel support from PharmaMar and
Roche. SP received honoraria from Roche, AstraZeneca, MSD,
Pfizer and PharmaMar. ADB received honoraria from Roche,
Astra Zeneca, PharmaMar, Tesaro, Pfizer, and Advaxis. PH has
received honoraria from Astra Zeneca, Roche, Tessaro, Clovis,
PharmaMar. SCC has received honoraria from Roche, AZ,
PharmaMar.
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Volume 28 | Supplement 8 | November 2017