ut

o
i th
Systemic Management of Ovarian w Cancer
O
t e ES
and Inhibitors ofibPARP u d
s t r a n
i
d o r
r
o uth
Jan B. a te e a MD, PhD
Vermorken,
l i c ofthMedical Oncology
p of
Department
u
t dAntwerp University Hospital
n
o o
n issi Edegem, Belgium
o
D rm
pe
Online ESO-ESMO Masterclasses (Western/Central Europe, Arab/Southern Europe & Latin America), 2021
 Conflict of Interest Disclosure ut
o
i th
w O
t e ES
i b u d
• Participates in Advisory Boards of:
s t r a n
i
d KGaA, r
Innate Pharma, Merck r h o Merck Sharp &
Dome Corp, e
o ut PCI Biotech,
Nanobiotix,
a t a
WntResearch
l i c h e
p of t
•
u
dfrom:n
o t
Lecturer fee
io
n Merck-Serono,
iss Sanofi, BMS, MSD
o
D rm
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 Epithelial Ovarian Cancer (EOC) ut
o
Introduction ith w O
• Most lethal gynecological cancer t e ES
i b u d
• Globally, 239.000 new cases, 152.000
s t r will
a ndie
- 7th most most common cancerdi r
- 8th most common cause ofocancer r thdeath o in women
- 2nd most common cause t u
e of gynecologic
a cancer death
i c a h e
• p
Genomic predisposition l f
to tEOC in up to 15% (BRCA1 and
BRCA2 identifiedd u o
as causative genes in 65-75%)
o t o n
• n no.issofi lifetime ovulations, family history, smoking,
Risk factors:
benign o
D gynecologic
m conditions, potentially talcum powder use
r
pe
Lheureux et al, Lancet 2019; 393: 1240-1253
 Epithelial Ovarian Cancer (EOC) ut
o
Introduction ith w O
• More than two-thirds of patients diagnosed t eat advanced
E S stage
i b u d
• More than 90% of malignant ovarian
s t r tumors n are of epithelial
a cancer (EOC)
i
d o
origin, and are designated epithelial r
ovarian
o r t h
• Most common and most lethal
t e EOC a u is high grade serous
carcinoma (HGSC) ca e
l i
pHGSC t h
• u
Most extra-uterine o f arise from the fallopian tube (FT), i.e.
d n mucosal carcinoma in tube w/wo
STIC present,t or invasive
o io
n partially/entirely
s
STIC, or FT
o is incorporated in tubo-ovarian mass*
D rm
pe
Lheureux et al, Lancet 2019; 393: 1240-1253
Colombo et al, Ann Oncol 2019; 30: 672-705
*Differentiate from ovarian origin (No STIC or invasive mucosal carcinoma in either tube in presence of ovarian mass or
microscopic ovarian involvement), from primary peritoneal HGSC and from tuba-ovarian origin
HGSC= high-grade serous carcinoma; STIC= serous tubal intraepithelial carcinoma
 Epithelial Ovarian Cancer (EOC):t
Diagnosis o u
th i
w O
• EOC symptoms are not specific t e ES
abdominal bloating, early satiety, nausea, i b u d
abdominal distension,
s t r
change in bowel function, urinary isymptoms, a n back pain, fatigue
d o r
and loss of weight r
o ut h
t e a
• a
Investigations include cCA125
i e
and pelvic ultrasound
Additionally: chest p l f th / pelvic CT (pelvic MRI)
/ abdomen
d u o
o t o n
i surgery done by a well trained gynecological
• Staging is n s
surgical:
o is
D surgeon,
oncology
r m with the goal of no residual disease
pe
Lheureux S et al, Lancet 2019; 393: 1240-1253
 Epithelial Ovarian Cancer t
Milestones in therapy hou
i t
• w O
Surgery according to FIGO guidelines
t e ES
– LND and peritoneal staging in early
i b u
ovarian cancer
d
– Upfront maximal surgical debulking s t r n
inaadvanced
d i r
ovarian cancer r h o
o ut
t e a
• a
Evolution in systemicctherapy
i h e
– Introduction of
l
pplatinum t
f compounds and taxanes
u o
d chemotherapy
o t
– Intraperitoneal
io n
n iss
– Targeted therapy (antiangiogenic compounds and
PARP
o
D inhibitors)
m
r
pe
 FIGO Staging (2017) of Ovarian, Fallopian
t
Tube and Primary Peritoneal Carcinoma
u
h o
IA Confined to one ovary, intact capsule, no tumor on surfaceit(Ov;FT), no
malignant cells in ascites or peritoneal washings w O
Confirmed to both ovaries (same criteria as IA) te S
IB
IA or IB + surgical spill/capsule rupture/tumor b onu
E
IC
r i d
surface/pos. cells
Extension a/o implants on uterus a/o FT(s)ta/o ovary(ies) n
IIA
i s r a the pelvis
IIB d
Extension to other pelvic tissues, including
r oPPC with confirmed spread to
bowel within
III Tumor involves one or both ovaries or FTs or
peritoneum outside pelvis a/oe
h
o utto retroperitoneal lymph nodes
IIIA1i LN metastasis ≤ 10 mm inagreatest a
t ediameter
metastases

IIIA1ii LN metastasis > 10 mm l i cin greatest

t h diameter
IIIA2 u p involvement
Microscopic extrapelvic
o f w/wo RPLN, including bowel
involvement d n
IIIB Macroscopic o t io
peritoneal metastases beyond pelvis, ≤ 2 cm in diameter,
includingnbowel s s
D o i involvement w/wo RPLN
IIIC Peritoneal
r m
metastases beyond pelvic brim > 2 cm w/wo RPLN metastases
IVA
IVB
e
Pleural metastases
Parenchymal
with positive cytology
p metastases and metastases to extra-abdominal organs
 Epithelial Ovarian Cancer: Subtypes
t
o u
HGSC CCC EC
i th MC LGSC
Percentages:
w O
FIGO I-II 39% 33%
t e ES
22% 5% 1%
FIGO III-IV
Genetic Risk
86%
BRCA1/2
2%
HNPCC
i b u 7%

d
HNPCC
2%
None known
3%
None known
Other Risk  Risk with OC,
s t r a n
 Risk with OC,
Factors pregnancy i
None known
d o r
 Risk with HRT
None known None known

Precursors STIC r
o uth
Endometriosis Endometriosis Unknown SBT

t e a
Presentation

i c a
Ascites, GI sxs

h e
Adnexal mass Adnexal mass Adnexal mass GI sxs

Pattern of l
p of
Peritoneal, tPeritoneal, Peritoneal, Peritoneal +/- Peritoneal,
Spread
unodal
d n
nodal, distal nodal, distal Pseudomyxoma nodal
Chemotherapy
Response
o t
Sensitive, then

io
resistant
Resistant Sensitive Resistant Resistant

n iss PTEN, 
Molecular
Genetics o
D rm
p53, BRCA1/2,
PI3K, HRD
PI3K, ARID1A,
MSI
catenin,
ARID1A, MSI
KRAS, HER2
BRAF, KRAS,
NRAS

pe
PARP, BRAF,
Targets Angiogenesis ER, PR, mTOR HER2/neu
Angiogenesis MEK/ERK

Valencia Meeting 2015 (Bookman)

Management of Early-Stage Ovarian Cancer
t
FIGO I-IIa o u
h i t
Grade and completeness of staging arete
w O
•
u
the most
E S strongest
prognostic factors
ri b nd
• i s t a as an adjuvant
Low risk patients do not need chemotherapy
d r
treatment (5-yr survival ≥ 95%) thor
o u
• High-risk patients do a te adjuvant
need e
a platinum-based IV
chemotherapy: combinedl i c t h
analysis of ICON-1 and ACTION
trial* showed d
p
u OSo82%vs
5-yr
f 74%, p=.008
t
o cycles o n
i (GOG0157): no significant difference in
• Three vsnsix s
o
outcome, butis
recurrence rate with 6 cycles was 24% lower
D r m
than with
p e 3 cycles, and significantly more toxic**
*Trimbos et al, J Natl Cancer Inst 2003; 95: 113-125 **Bell et al, Gynecol Oncol 2006; 102: 432-439
 GOG0157: Histologic Subsets t
o u
i th
w O
t e ES
i b u d
s t r a n
i
d should r
• “Early-Stage”rHGSC
h o be treated similar to
advanced-stage o HGSC.
u t
t e a
• The role
i c a of adjuvant chemotherapy in early-
h e
l
stage
p of t
non-HGSC remains to be established.
u
d n
o t io
n iss
o
D rm
pe
Chan JK, et al. Gynecol Oncol 2010; 116: 301-306
Management of Advanced Epithelial Ovarian Cancer
t
Stages IIb-IV ou
i th
w O
t e ES
i b u d
s t r a n
i
d o r
r
o uth
t e a
i c a h e
l
p of t
u
d n
o t io
n iss
o
D rm
pe
5th Ovarian Cancer Consensus Conference, Tokyo, Japan, November 2015
NCCN Guidelines Insight. Ovarian Cancer, version 1.2019, J Natl Compr Canc Netw 2019; 17: 896-909
(Courtesy of Antonio González Martin)
 Prognostic Factors in Advanced-Stage Ovarian Cancer
Stages IIb-IV u t
ho
i t
Postsurgery During wRelapseO
Pre-chemotherapy Chemo t e ES
i b u d
• Residual disease t
Type of chemo
s r n
a Disease bulk
Time since last CT
• Performance status d
CA 125 i fall** r
• Stage r h o
o t
Interval debulking
u
Histology
• Grade
t e a No. disease sites
• Age
i c a h e Perf. status
• Ascites
p l f t Time since DX
• Histology u
d n o
o t
• Proliferation markers
io
• Quantitativen pathol.
iss features
• Ploidy o
D markers*
• Molecular r m
pe
Eisenhauer EE et al. Ann Oncol 1999; 10: S9-S15 (modified)
*Bookman MA et al. Ann Oncol 2017; 28 (suppl): viii30-viii35 (including gBRCA1/2 and sBRCA1/2)
** McGee J et al. Ann Oncol 2017; 28: 702-710 (A failure of HE4 to normalize at completion of treatment indicator of poor prognosis)
 ut
Advanced Epithelial Ovarian Cancer
o
1998-2021 Treatment ith
w O
t e ES
• i b u d
3-wkly IV paclitaxel (175 mg/m ) + IV
s t r carboplatin
a n 2
(AUC 5-6)
– Generally agreed standard i r
r d o trials*
– “Control Arm” of most recent o ut h
randomized
– No other regimen shown t e to outperform
a it
i c a h e
l
p of t
u
d far from
• t
However, results
o io n perfect:
n s
– Median TTP:s12-18 mo
i
o
D OS:
– 5-Year m <35%
r
pe
*Bookman MA et al, Ann Oncol 2017; 28 (suppl 8): viii30-viii35 (Report of 5th OCCC, Tokyo, Japan [2015])
 Systemic Therapy for Ovarian Cancert2020
o u
NCCN Guidelines: OC, version 2.2020
h i t
• Three-weekly paclitaxel/carboplatin (TC) standard w chemotherapy
O
for first-line therapy in advanced OC (1998-2021) t e ES
i b u d
s t r a n
• Acceptable alternative schedules a/o route i
d o r
of administration

-TC + bevacizumab → bevacizumab

r th or GOG-218)
o (peruICON-7
t e a(AUC 5-6)
i c a 2
- Docetaxel (60-75 mg/m ) / carboplatin
h e
l
- Paclitaxel weekly (80 mg/m
t
2
) / carboplatin weekly (AUC 2)
p oIVf carboplatin (JGOG#3016)
- Paclitaxel weekly / 3-weekly
d u 2
t ion chemotherapy (IPCT) in stage III
- Pegylated liposomal dox. (30 mg/m ) / carboplatin (AUC 5)
- Intraperitonealoplatinum-based
patients afternprimary
s s
- HIPECD o be m
can i surgery with <1 cm residual disease*
considered during IDS in stage III after NACT*
r
pe
HIPEC= hyperthermic intraperitoneal chemotherapy, NACT= neoadjuvant chemotherapy
*Not endorsed in the ESMO-ESGO conference (Milan 2018)
 Targeted Therapies in Ovarian Cancer
u t
Target Drug(s) o
i th
wcanertinib,
O
ErbB kinases
t e ES cetuximab,
Gefitinib, erlotinib, lapatinib,
pertuzumab, matuzumab,
i b u d
trastuzumab
MUC1 / PEM Pemtumomabist
r a n
d o r
MUC16 (CA 125) Oregovomab
o r t h
mTOR / AKT
t e aueverolimus, deforolimus
Temsirolimus,

i c a h e
PARP
p l ft
Olaparib, veliparib, niraparib, rucaparib
EpCAM
d u o
Catumaxomab

o
Apoptosis pathway t io nAEG35156, OGX-011
n i s
s Bevacizumab,
o
Angiogenesis
D rm
sunitinib, sorafenib, pazopanib,
cediranib, vatalanib
e
Endothelialpcells Combretastatin, Oxi4503
Matrix metalloproteinases BAY 12-9566, marimastat
Recommended Guidelines for Chemotherapy
t
ou
in Relapsed Ovarian Cancer (ROC)
i th
w O
Partially Platinum te S
Platinum
sensitive bu
E Fully Platinum
resistant
t ri n d sensitive

i s r a
r d o
Platinum-free o t h
interval <6 months
t e a u
6-12 months >12 months

i c a h e
l
p of t
u
d n
o t
Non-platinum
single agent: i o Combination Carboplatin
n iss chemotherapy: combination:
PLD,owkl paclitaxel,
Dgemcitabine,
r m Platinum-based or PLD, paclitaxel,

p e
topotecan
trabectedin-PLD gemcitabine

E.Pujade-Laurain; Ann Oncol 2016; 27 (suppl.1): i63-i65 PLD: pegylated liposomal doxorubicin
 t
Trials of Anti-Angiogenic Therapy inuROC
ho
i t
Platinum-refractory/resistant w O
• AURELIA trial* t e ES
− Single agent non-Pt vs non-Pt+bev→PFS↑ i b u d with combo
• MITO-11 trial** s t r a n
− Wkly paclitaxel vs same plus d
i r
r o
pazopanib→
h PFS↑ with combo
Platinum-sensitive disease o u t
• OCEANS trial t e a
i c a +

h e
− GCx6 vs GC/bevx6 l
p of → bevacizumab
t maintenance→PFS↑
• ICON 6 trial u ++
d vs nPt-based CTx6 plus cediranib vs
o t
− Pt-based CTx6
io
n CTx6+cediranib→cediranib
Pt-based
iss maintenance→PFS↑.
o
D rm
pe
*Pujade-Lauraine E et al. J Clin Oncol 2014; 32: 1302-1308
**PignataS et al. Lancet Oncol 2015; 16: 561-568
+Aghajanian C, et al. J Clin Oncol 2012; 30: 20139-2045
++Ledermann J, et al. Lancet 2016; 387: 1066-1074
 ut
Bevacizumab in Primary Therapy for Ovarian
o
ith
Cancer with Maintenance: Efficacy
w O
GOG 218 First lineu ICON
t e E S 7 First line
ri b n d
with maintenance
i s t with maintenance
a PFS (RECIST)
1 2

Primary endpoint d
PFS (RECIST/CA125/
o r
Clinical
o r t h
Secondary endpoint OS te a u OS, RR
Maintenance duration
i
15c a
monthsemaximum
h 12 months maximum
Stopping rules
l
p GCIG f t
(CA125) RECIST progression
d u o
Results (∆PFS)
o t io n
6 months 5.4 months
(high risk group)
n iss NS
o
Results (OS)
D rm
NS

1Burger
pe
et al. N Engl J Medicine 2011; 356: 2473-2483 and Burger et al J. Clin Oncol 36 (15S), abstr#5517 ( relative HR for
stage IV patients was reduced with Bev throughout compared to control (HR 0.774)
2Perren et al. N Engl J Medicine 2011: 365: 2484-2496
Bevacizumab in Primary Therapy for
t
o
Ovarian Cancer with Maintenanceu
h i t
w O
t e ES
i b u d
s t r a n
i
d o r
r
o uth
t e a
i c a h e
l
p of t
u
d n
o t io
n iss
o
D rm
pe
Perren et al. N Engl J Medicine 2011: 365: 2484-2496
 ut
Bevacizumab in Primary Therapy for Ovarian
o
ith
Cancer with Maintenance: Toxicity
w O
GOG 218 Firstline u ICON t e E S7Firstline
ri b nwithd
with maintenance t
SelectedisAE (≥G3
maintenance
aunless specified)
1 2

d o r
o r t h
GI perforation (≥G2) t e0.2% au 1.3%
Proteinuria
i c a h
1.6%e 1.0%
Hypertension (≥G2) p l f t
22.9% 18.0%
d u o n/r
Diarrhea
o t io n 0.0%
Liver toxicity
n iss n/r 0.0%

D rmo
pe
1Burger et al. N Engl J Medicine 2011; 356: 2473-2483 and Burger et al J. Clin Oncol 36 (15S), abstr# 5517
2Perren et al. N Engl J Medicine 2011: 365: 2484-2496
 ut
o
i th
w O
t e ES
i b u d
s t r a n
i
d o r
r
o uth
t e a
i c a h e
l
p of t
u
d n
o t io
n iss
o
D rm
pe
O’Connor MJ. Mol Cell 2015; 60: 547-560
 t
PARP Inhibition Activity Extends beyond
u
non-BRCA HRR Deficiency (HRD) o
th i
w O
t e ES
i b u d
s t r a n
i
d o r
r
o uth
t e a
i c a h e
l
p of t
u
d n
o t io
n iss
o
D rm
pe
Konstantinopoulos PA et al. Cancer Discov 2015; 5: 1-18
Maintenance Trials: Building on the Benefit
t
o
of Standard of Care Chemotherapy u
h i t
w O
t e ES
i b u d
s t r a n
i
d o r
r
o uth
t e a
i c a h e
l
p of t
u
d n
o t io
n iss
o
D rm
pe
Ledermann J, et al. N Engl J Med 2012;366:1382–1392; Pujade-Lauraine E, et al. Lancet Oncol 2017; 18: 1274-1284; Mirza
MR, et al. N Engl J Medicine 2016; 375: 2154-2164; Coleman RL et al. Lancet 2017; 390: 1949-1961
 Study 19 (Olaparib) u t
o
i th
w O
t e E S
Study aim and design
i b u 265
d patients
Patients: s t r a n
i
d 400 rOlaparib
r
• Platinum-sensitive high-grade serous
h o mg po bid Treatment
ovarian cancer o ut
t e a Randomized 1:1 until

i a
• 2 previous platinum regimens
c th e disease
l
• Last chemotherapy was platinum-based
p of PR or Placebo Progression
to which they had a u
maintained
t d
CR prior to enrolment n po bid

• Stable CA-125
o
n issi o
o
D rm Primary end point : PFS

pe
Ledermann J, et al. N Engl J Med 2012;366:1382–1392;
 Study 19 (Olaparib) ut
o
i th
w O
t e ES
i b u d
s t r a n
i
d o r
r
o uth
t e a
i c a h e
l
p of t
u
d n
o t io
n iss
o
D rm
pe
Adverse events more commonly reported in the olaparib group than in the placebo (by more than 10% of patients):
nausea 68% vs 35%, fatigue 49% vs 38%, vomiting 32% vs 14%,anemia 17% vs 5% (majority grade 1 or 2)

Ledermann J, et al. N Engl J Med 2012; 366: 1382-1392

 Retrospective Analysis in Study 19
PFS in BRCA mutated patientsut
ho
i t
w O
t e ES
i b u d
s t r a n
i
d o r
HR 0.18 (95% CI: 0.10-0.31)

r
o uth
t e a
i c a h e
l
p of t
u
d n
o t io
n iss
o
D rm
pe
Ledermann et al. Lancet Oncol. 2014;15(8):852–861
 ut
Confirmatory Studies in Platinum-Sensitive
o
Recurrent Ovarian Cancer*ith w O
SOLO2 1
NOVA t e EARIEL3
S 2 3

Niraparibi b u d
Olaparib
s t r a n Rucaparib

d i r
rPt-S ROCo
Study population Pt-S ROC
t
o all-comersh Pt-S ROC
BRCAm
t e a u with capped tBRCA

i c a h e
Inclusion l
HGSOC/HGEOC
pPt regimes t HGSOC HGSOC/HGEOC
f ≥2 prior Pt regimes ≥2 prior Pt regimes
u
≥2 prior
o
d tonlast Pt CR/PR to last Pt CR/PR to last Pt
o t
CR/PR
io
n iss
mPFS (months)o
D rm
19.1 vs 5.5 21.0 vs 5.5 16.6 vs 5.4 (gBRCA) (BRCAm)
12.9 vs 3.8 13.6 vs 5.4 (non-gBRCA) (HRD)

pe
1Pujade-Lauraine
10.8 vs 5.4 (ITT popul)
E, et al. Lancet Oncol 2017; 18: 1274-1284; 2Mirza MR, et al. N Engl J Medicine 2016; 375: 2154-2164;
3Coleman RL et al. Lancet 2017; 390: 1949-1961*Phase III trials
 ut
BRCA1/2 Mutations: Biomarker of Activity of
ho
PARP Inhibition it w O
t e Pt-SErelapsed
S
Hazard ratio for PFS benefit in maintenance studies
i u
b ndin disease

s t r a
d i
BRCA mutant r BRCA wild type
r h o
o ut
t e a0.18
Study 19 (olaparib)
i a
c th e 0.54

NOVA (niraparib) p l f 0.27 0.45*

d u o
ARIEL3 (rucaparib)
o t o n 0.23 0.44 / 0.43
n issi
o
D rm Pt response defines this group

pe
Ledermann J, et al. NEJM 2012; Mirza MR, et al. NEJM 2017; Coleman RL, et al. Lancet 2017;
Ledermann J, et al. Lancet Oncol 2020
Courtesy of J Ledermann
Algorithm for the Treatment of Patients with
Recurrent Ovarian Cancer t
o u
i th
w O
t e ES
i b u d
s t r a n
i
d o r
r
o uth
t e a
i c a h e
l
p of t
u
d n
o t io
n iss
o
D rm
pe
Colombo N et al. for theESMO-ESGO Ovarian Cancer Consensus Conference Working Group. Ann Oncol 2019; 30: 672-705
 PARP-inhibitors Moving to First-Line* u t
o
i th
Study PARPi Type of study w O
t e ES
i b u d
VELIA s t r
veliparib TC+placebo→placebo a n vs
d i r →placebo vs
TC+veliparib
r o
o uth
TC+veliparib→veliparib
PAOLA-1
e a
olaparibat TC+Bev→Bev+olaparib vs
l i h e
c tTC+Bev→Bev+ placebo
u p of
SOLO-1
t d olaparib Olaparib vs placebo maintenance
n
n o s io in BRCAm OC after Pt-based CT
PRIMA o isniraparib Niraparib vs placebo maintenance
D rm in OC after response to Pt-based CT
pe
Moore, N Engl J Med, 2018; 379: 2495-2505
Ray-Coquard, ESMO 2019
PARPi in First-Line Epithelial Ovarian Cancer
t
Results ou h
VELIA:Veliparib throughout vs chemotherapy i t
w O
- BRCA1/2-mut: 34.7 vs 22.0 mo;
t e ES
HR 0.44, p<0.001
HR 0.57,up<0.001
- HRD-positive:
- ITT population:
31.9 vs 20.5 mo;
23.5 vs 17.3 mo; rib p<0.001
HR t0.68, n d
- HRD-negative: 15.0 vs 11.5 mo; i
HR s a CI 0.60 to 1.09
0.81,r95%
d o after CT+ bevacizumab
PAOLA-1: olaparib + bevacizumab vsrbevacizumab
o t h
- ITT population: 22.1 vs 16.6 mo;
t e HR
a u 0.59, p<0.0001
- HRD-positive: 37.2 vs 17.7
i a mo;
c16.2 mo;h e HR 0.33, p<0.0001
- HRD-negative: l
16.6 vs
p maintenance
f t HR 1:00, 95% CI 0.75 to 1.35
u
SOLO-1: olaparib vs placebo o
- BRCA-mutated: t d NR vs n 13.8 mo; HR 0.30, p<0.001
o io
n vsisplacebo
PRIMA: nirapanib s maintenance
o
- HRD-positive: 21.9 vs 10.4 mo; HR 0.43, p<0.001
D rm 13.8 vs 8.2 mo; HR 0.62, p<0.001
- ITT population:
pe 8.1 vs 5.4 mo; HR 0.68, p=0.02
- HRD-negative:

Modified from Banerjee S et al. ESMO open 2020; 5: e001110.

 PARPi Trials in Maintenance OC Treatment
t
Compliance and toxicity ho u
i t
w O
Agent Study G 3-4 Dose Dose
TRAE Interrup Reduct u
t
Dosee S
MDS/
Discont E AML
Treatm.
Deaths
ri b nd
i s t a
Olaparib Study 19 35.3% 27.9% 22.8%
r2.2%
d o 11.0% 2.0%
36.0% 45.0% r 25.0%
2.0% 0%
SOLO2
o t h 1.0%
SOLO1
t
39.0% 52.0% u 12.0% 1.0%
e a28.0% 0%
64.6%ca68.9% e 66.5%
Niraparib NOVA
p l i t h 14.7% 1.4% 0.3%
PRIMA 65.3% f
79.5% 70.9%
u 64.0% 55.0% 13.0% 1.0% 12.0% 0.3% 0%
Rucaparib Ariel3 d 56.0% o
o t o n
i 41.0% 24.0% 19.0% 0.2%
1.0%
Veliparib
n
VELIA
s
88%
Olaparib/ oPAOLA-1is57.0% 54.0% 41.0% 41.0% 1.0%
0%
0%
Bev D rm
pe
Modified from Gogineni et al. J Cancer 2021; 12: 38-53
 SOLO-1: Progression-free Survival
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Moore K, et al, N Engl J Med, 2018; 379: 2495-2505
 t
PAOLA-1 Progression-free Survival
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Ray-Coquard I et al. N Engl J Med, 2019; 381: 2416-28
 ut
Immunotherapy in Epithelial Ovarian hocancer*
i t
w O
t e E S
• Single agent CPI
i u
b from d
Response rates to CPIs are low, ranging
s t r a n 6% to 22%
Some impressive prolonged responses i
d o r
r
o uth
• Multimodality immunotherapy t e (IT) a strategies:
i c a h e
- IT with chemotherapyl
p of t
- IT with other ITuagents
t d n therapy
- IT with antiangiogenic
o io
n isinhibitors
- IT with PARP s
o m+ antiangiogenic therapy
- IT +DPARPi
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*Levinson et al. 2019 ASCO Eductional Book
 Take-Home Messages (1) ut
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• Upfront surgery ➔6 x TC-based CT standard t e forESadvanced OC
i b u d
• s t r n
forasome patients
NACT with IDS reasonable alternative
d i r
r h o
• Three-weekly paclitaxel/carboplatino ut(TC) w/wo bevacizumab
t e a
i c a
(depending on patient/disease
h e characteristics) standard
l
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• d u
Intraperitoneal chemotherapy and HIPEC can be considered in
o t io n
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specific situations
D o m
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PARP inhibitors have established a new standard of care
p
 Take-Home Messages (2) ut
o
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t e maintenance
E S
• Olaparib, nirapanib and rucaparib are of benefit
i u as
b and d
t
therapy in platinum-sensitive high-grade serous
s r n endometrioid
a BRCA1/2 mutations
i
recurrent ovarian cancer, in particular patients
d o r with

•
r
o uth therapy in patients with
Olaparib approved as first-line maintenance
t e a
BRCA1/2 mutation
i c a h e
•
l t
p oasf first-line maintenance therapy
u
Niraparib recently approved
d nstatus
o t
irrespective of biomarker
io
n iss with bevacizumab as maintenance approved in
• o
Olaparib in combination
D rmadvanced ovarian cancer
HRD-associated
pe
 UZA

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DIAMOND

h e
DESIGN

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Thank you
 ut
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