Epithelial Ovarian Cancer

Jan B. Vermorken, MD, PhD

Department of Medical Oncology

Antwerp University Hospital

Edegem, Belgium

17th ESO-ESMO Masterclass in Clinical Oncology, Nauen OT Gross Behnitz (Berlin), Germany, March 24-29, 2018

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Conflict of Interest Disclosure

• Participates in Advisory Boards of:

Amgen, AstraZeneca, Boehringer Ingelheim,

Innate Pharma, Merck KGaA, Merck Sharp &

Dome Corp, PCI Biotech, Synthon

Biopharmaceuticals,

• Lecturer fee from:

Merck-Serono, Sanofi, Bristol Myers Squibb

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Outline

• Epidemiology, risk factors, pathology and staging

• Standard management of early and advanced EOC

• Various ways to improve results beyond PAC-CARBO

• Potential roles of targeted therapies

• Types of relapsed ovarian cancer

• Strategies towards treatment of relapsed disease

• Take-home messages

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Epithelial Ovarian Cancer

Epidemiology

• Life-time risk is 1 in 54

• The crude incidence of ovarian cancer in the European

Union is 18/100.000 women per year, the mortality is

12/100.000 women per year

• The median age at diagnosis is 63 years. The incidence

increases with age and peaks in the 8th decade.

Between the age of 70-74 years the age-specific

incidence is 57/100.000 women per year

* ESMO minimum Clinical Recommendations 2008 and 2013 (Ann Oncol )

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Epithelial Ovarian Cancer

Risk factors

• Age, older↑ Multiple pregnancies↓

• Nulliparity↑ Breast feeding↓

• Early menarche↑ Oral contraceptives↓

• Late menopause↑ Tubal ligation↓

• Obesity and use of talcum

• Positive family history

- first degree relative with OC→ 2 fold increased risk

• BRCA-1 mutation →15%-45% OC risk (≤85% BC risk)

• BRCA-2 mutation→10%-20% OC risk (≤85% BC risk)

Ledermann et al. Ann Oncol 2013; 24 (suppl.6): vi24-vi32) 17th E

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Ovarian Cancer

Pathology

Common “Epithelial” Tumors

• Serous

• Endometrioid

• Clear cell

• Mucinous

• Brenner (transitional cell)

• Mixed epithelial tumors

• Undifferentiated

• Unclassified

Scully RE, Sobin LH, Serov SF, 1999 (WHO classification of Ovarian Epithelial Tumors)

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Molecular Pathogenis in Ovarian Cancer

• Type 1* – Low grade – Early stage – Slow growing

– Resistant to platinum-based therapy

– KRAS, BRAF, ERBB2, PTEN, PIK3A, ARID1A mu

– IGFR expression

– Wild-type p53

• Type 2** – High grade – Advanced stage – Agressive

– Responsive to platinum-based therapy

– Frequently associated with TP53 mutations

– BRCA1/2 mutations (20%)

– Activation of the PI3K pathway

*Low grade serous, endometrioid, mucinous, clear cell and malignant Brenner: ** HGSC, HGEC, malignant MMT

and undifferentiated tumors

Bast Jr RC, Ann Oncol 2011 (Suppl 8): viii5-viii15; Ledermann JA, Ann Oncol 2013 (Suppl 6): vi24-vi32

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Epithelial Ovarian Cancer: Subtypes

HGSC CCC EC MC LGSC

Percentages:

FIGO I-II

FIGO III-IV

39%

86%

33%

2%

22%

7%

5%

2%

1%

3%

Genetic Risk BRCA1/2 HNPCC HNPCC None known None known

Other Risk

Factors

Risk with OC,

pregnancy None known

Risk with OC,

Risk with HRT None known None known

Precursors STIC Endometriosis Endometriosis Unknown SBT

Presentation Ascites, GI sxs Adnexal mass Adnexal mass Adnexal mass GI sxs

Pattern of

Spread

Peritoneal,

nodal

Peritoneal,

nodal, distal

Peritoneal,

nodal, distal

Peritoneal +/-

Pseudomyxoma

Peritoneal,

nodal

Chemotherapy

Response

Sensitive, then

resistant Resistant Sensitive Resistant Resistant

Molecular

Genetics

p53, BRCA1/2,

PI3K, HRD

PI3K, ARID1A,

MSI

PTEN,

catenin,

ARID1A, MSI

KRAS, HER2 BRAF, KRAS,

NRAS

Targets PARP,

Angiogenesis Angiogenesis ER, PR, mTOR HER2/neu

BRAF,

MEK/ERK

Valencia Meeting 2015 (Bookman) 17th E

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Ovarian Cancer: FIGO Staging

Surgical exploration

Diagnostic

• Vertical incision

• Peritoneal fluid cytology (or saline irrigation)

• Scrupulous inspection - right diaphragm

- liver, serosa, parenchyma

• Biopsies of contralateral ovary, retroperitoneal LN and suspicious changes on the peritoneum, omentum

Therapeutic

• Early disease – TAH + BSO, omentectomy, LND

• Advanced disease – debulking surgery

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FIGO Staging (2008) Ovarian Cancer

IA Confirmed to one ovary, no ascites, intact capsule

IB Confirmed to both ovaries (same criteria as IA)

IC IA or IB + tumor surface/capsule rupture/pos. cells

IIA Extension to the uterus or tubes

IIB Extension to other pelvic tissues

IIC IIA or IIB + tumor surface/capsule rupture/pos. cells

III One or both ovaries + extension outside pelvis or limited

to true pelvis + extension to small bowel or omentum

IIIA LN Θ, extension only microscopically

IIIB LN Θ, extension not exceeding 2 cm in diameter

IIIC LN + (RP/inguinal) and/or extension >2 cm in diameter

IV One or both ovaries + DM (or parenchymal liver mets) 17th E

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Epithelial Ovarian Cancer

Milestones

• Surgery according to FIGO guidelines

– At least LND and peritoneal staging in early

ovarian cancer

– Upfront maximal surgical debulking in advanced

ovarian cancer

• Chemotherapy evolution

– Introduction of platinum compounds

– Introduction of taxanes

• The set-up of international collaboration (1997)

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Management of Early-Stage Ovarian Cancer

FIGO I-IIa

• Grade and completeness of staging are the most strongest

prognostic factors

• Low risk patients do not need chemotherapy as an adjuvant

treatment (5-yr survival ≥ 95%)

• High-risk patients do need adjuvant platinum-based

chemotherapy: combined analysis of ICON-1 and ACTION

trial* showed 5-yr OS 82%vs 74%, p=.008

• Three vs six cycles: no significant difference in outcome,

but recurrence rate with 6 cycles was 24% lower than with 3

cycles, and significantly more toxic**

*Trimbos et al, JNCI 2003; **Bell et al, Gynecol Oncol 2006

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GOG0157: Histologic Subsets

Chan JK, et al. Gynecol Oncol 116:301-6, 2010

• “Early-Stage” HGSC should be treated similar to

advanced-stage HGSC.

• The role of adjuvant chemotherapy in early-

stage non-HGSC remains to be established.

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Management of Advanced-Stage Ovarian

Cancer

Stages IIb-III (IV)

• Upfront radical cytoreductive surgery*

• In case this is not possible, a second attempt should be made

• Platinum-taxane based chemotherapy

• Six cycles

• No second-look

2nd Consensus Meeting 1998 Bergen (The Netherlands)

*5th Consensus Meeting 2015 Tokyo (Japan): PCS or NACT→±ICS 17th E

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Prognostic Factors in Advanced-Stage Ovarian Cancer

Stages IIb-IV

Postsurgery During Relapse

Pre-chemotherapy Chemo

• Residual disease Type of chemo Time since last CT

• Performance status CA 125 fall** Disease bulk

• Stage Interval debulking Histology

• Grade No. disease sites

• Age Perf. Status

• Ascites Time since DX

• Histology

• Proliferation markers

• Quantitative pathol. features

• Ploidy

• Molecular markers*

Eisenhauer EE et al. Ann Oncol 1999 (modified)

*Bookman MA et al. Ann Oncol 2017 (including gBRCA1/2 and sBRCA1/2)

** McGee J et al. Ann Oncol 2017 (A failure of HE4 to normalize at completion of treatment indicator of poor prognosis)

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Bookman, M. A. et al. J Clin Oncol 2009

Optimal Cytoreduction after PDS the Most

Important Prognostic Factor in ADOVCA

Du Bois et al. Cancer 2009

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Stage III Disease: Role of Histology

Winter WE, J Clin Oncol 25:3621-3627, 2007

Data from GOG 111, 114,132, 142,158, 172 (IV only)

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Advanced Ovarian Cancer

1998-2018 Treatment

• 3-weekly paclitaxel + carboplatin (TC)

– Generally agreed standard

– “Control Arm” of most recent randomized trials*

– No other regimen shown to outperform it

• However, results far from perfect:

– Median TTP: 12-18 mo

– 5-Year OS: <35%

*Bookman MA et al, Ann Oncol 2017; 28 (suppl 8): viii30-viii35 (Report of 5th OCCC, Tokyo, Japan [2015]); 17th ESO-E

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How to Improve Outcome in Advanced OC

Beyond PAC-CARBO

• Increase rate of optimal cytoreduction

– NACT followed by IDS of benefit for some patients

• Increase efficacy of cytotoxic chemotherapy

– Adding a third cytotoxic drug → no OS benefit

– Maintenance/consolidation with cytotoxics→ no OS benefit

– Maintenance with targeted therapy improves PFS

– Dose-dense therapy with taxanes improves PFS/OS??

• Modulate resistance

– modulating agents no benefit in the clinic

– Intraperitoneal chemotherapy improves OS (12 mo in OD pts)

• The use of targeted therapies

− anti-angiogenic compounds and PARP inhibitors beneficial 17th ESO-E

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Selection of Patients for NACT

• Two trials of NACT-ICS vs PDS

in advanced stage III and IV

EOC→ similar poor outcome*

• NACT→ reduction in perioperative morbidity related to

- venous thromboembolism

- infection

- wound healing

• Candidates for NACT → bulky tumor deposits, large

volume ascites, advanced physiologic age, comorbidities

* Vergote et al. NEJM 2010; 363: 943-953 and Kehoe et al. JCO 2013; 31: (suppl; abstr 5500) 17th E

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Dose-Dense Weekly vs 3-weekly Paclitaxel

Randomized trials

Study Stages No. PFS/OS

JGOG II-IV 637 mPFS 28.0 vs 17.2 mo*

3-yr OS 72.1 vs 65.1%**

MITO-7 IC-IV 810 mPFS 17.3 (3 wkly) vs

18.3 mo (wkly)

MRC-UK ICON8 IC-IV 1556 mPFS 17.9 (3wkly) vs 20.6

(T wkly) vs 21.1 (TC wkly)

GOG262-ACRIN6695 II-IV 692 mPFS 14.7 vs 14.0 mo

*p=0.0015; **p=0.03 JGOG (Katsumata et al, Lancet 2009; MITO (Pignata et al, Lancet 2014; ICON8 (Clamp et al ESMO 2017):

GOG262-ACRIN6695 (NEJM 2016) 17th E

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IPCT vs IVCT in Advanced Ovarian Cancer

Overall survival

Investigators No. of Overall survival (mo)

year published pts Control arm Exp. Arm

Alberts et al, 1996 546 41 491

Polyzos et al, 1999 90 25 26

Gadducci et al, 2000 113 51 67

Markman et al, 2001 462 52 632

Yen et al, 2001 118 48 43

Armstrong et al, 2006 415 50 663

1 p = 0.02; 2 p = 0.05; 3 p = 0.03

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OS by Treatment and BRCA1 Expression

GOG 172

Lesnock JL et al Br J Cancer. 2013 108:1231-7 17th ESO-E

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IP Chemotherapy in ADOVCA

“It requires expertise and

should be standard of care for

optimally resected EOC

patients”

Vermorken JB. Ann Oncol 2006; 17 (suppl. 10): x241-x246

Walker JL. Ann Oncol 2013; 24 (suppl. 10): x41-x45 17th ESO-E

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Stage II to IV

ovarian, primary

peritoneal, or

fallopian tube

cancer

Including

suboptimal Cases

• Accrual: 655 pts (closed OCT2016)

• Primary Endpoint: PFS

• Secondary Endpoints: OS, Toxicity, QOL, Cost/Benefit

Paclitaxel 80 mg/m2/1h IV, weekly, Cycles 1-6

Carboplatin AUC 6 IV, Day 1, Cycles 1-6

Paclitaxel 80 mg/m2/1h IV, weekly, Cycles 1-6

Carboplatin AUC 6 IP, Day 1, Cycles 1-6

R

A

N

D

O

M

I

Z

E

iPocc Trial

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Studies with Neoadjuvant Chemotherapy

followed by IPCT or HIPEC

Provencher et al OV21/PETROC Van Driel et al. HIPEC study

Ann Oncol 2018; 29: 431-438 N Engl J Med 2018; 378;230-240

Arm 1: IV TC 3-weekly Three cycles NACT. When at least stable and debulkable

Arm 2: IP cisplatin + paclitaxel IV (d1) and IP (d8) to ≤ 10 mm → ICS either with or without HIPEC with

Arm 3: IP carboplatin + paclitaxel IV (d1) and IP (d8) cisplatin 100 mg/m2.

Primary endpoint PD9 arm 3 vs arm 1 (24.5% vs 38.6%; p=0.065) Primary endpoint: PFS (HR 0.66 95%CI 0.50-0.87;p=0.003) 17th E

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Targeted Therapies in Ovarian Cancer

Target Drug(s)

ErbB kinases Gefitinib, erlotinib, lapatinib, canertinib, cetuximab,

pertuzumab, matuzumab, trastuzumab

MUC1 / PEM Pemtumomab

MUC16 (CA 125) Oregovomab

mTOR / AKT Temsirolimus, everolimus, deforolimus

PARP Oleparib, veliparib, nirapanib

EpCAM Catumaxomab

Apoptosis pathway AEG35156, OGX-011

Angiogenesis Bevacizumab, sunitinib, sorafenib, pazopanib, cediranib, vatalanib

Endothelial cells Combretastatin, Oxi4503

Matrix metalloproteinases BAY 12-9566, marimastat 17th ESO-E

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Burger RA et al, N Engl J Med 2011; 365: 2473-2483

Primary and Subgroup Analysis of PFS

According to Treatment Group

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Primary Anti-vascular Therapy with

Maintenance or Only Maintenance in OC GOG 218 First Line

with Maintenance1

ICON 7 First Line

with Maintenance2

Pazopanib

Maintenance3

Primary

Endpoint

PFS (RECIST/CA

125/ clinical)

PFS (RECIST) PFS (RECIST)

Secondary

Endpoint

OS OS, RR OS, Safety, PFS

by GCIG, 3 yr

PFS, QOL

Maintenance

duration

15 months

maximum

12 months

maximum

24 months

maximum

Stopping rules GCIG (CA125) RECIST PD RECIST PD

Results (PFS in

∆ months)

6 months

(censored for

CA125 only events)

5.4 months

(high risk

subgroup)

5.6 months

Results (OS) NS NS (all stages) NS

1 = Burger et al. NEJM 356: 2011, 2 = Perren et al. NEJM 365: 2011, 3=Dubois et al. ASCO 2013 (LBA 5503)/JCO 32:2014

Presented by: Paul Sabbatini, MD; ASCO 2013 17th E

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ICON 7 Trial

Final Outcome Results

Oza et al Lancet Oncol 2015

Survival of ICON 7 by Risk Group

(High Risk: Residual disease >1 cm/ Stage IV)

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Primary Anti-vascular Therapy with

Maintenance or Only Maintenance in OC

GOG 218 First Line

with Maintenance1

ICON 7 First Line

with Maintenance2

Pazopanib

Maintenance3

Selected Adverse Events (> G 3 unless specified)

GI Perforation

(> G 2)

0.2% 1.3% 0

Proteinuria 2.2% 1 % 1%

HTN

(> G 2)

17 % 18 %

31 %

(grade ¾)

Diarrhea n/r 0% 8 %

Liver toxicity n/r 0% 9 %

Neutropenia 10 %

1 = Burger et al. NEJM 356: 2011, 2 = Perren et al. NEJM 365: 2011, 3=Dubois et al. LBA 5503 / JCO 2014 17th ESO-E

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Recurrent Ovarian Cancer

Vermorken JB. Second line randomized trials in epithelial ovarian cancer; Int J Gynecol Cancer 2008; vol. 18 (suppl. 1): 59-66 17th ESO-E

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Partially Platinum

sensitive

6-12 months

Recommended Guidelines for Chemotherapy

in Relapsed Ovarian Cancer

Fully Platinum

sensitive

>12 months

Combination

chemotherapy:

Platinum-based or

trabectedin-PLD

Carboplatin

combination:

PLD, paclitaxel,

gemcitabine

Platinum

resistant

Platinum-free

interval <6 months

Non-platinum

single agent:

PLD, wkl paclitaxel,

gemcitabine,

topotecan

PLD: pegylated liposomal doxorubicin Valencia Meeting 2015 (E.Pujade-Laurain)

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Trials of Anti-Angiogenic Therapy in ROC

Platinum-refractory/resistant

• AURELIA trial*

− Single agent non-Pt vs non-Pt+bev→PFS↑ with combo

• MITO-11 trial**

− Wkly paclitaxel vs same plus pazopanib→ PFS↑ with combo

Platinum-sensitive disease

• OCEANS trial +

− GCx6 vs GC/bevx6 → bevacizumab maintenance→PFS↑

• ICON 6 trial++

− Pt-based CTx6 vs Pt-based CTx6 plus cediranib vs

Pt-based CTx6+cediranib→cediranib maintenance→PFS↑.

)

* JCO 2014; **Lancet Oncol 2015; +JCO 2012; ++ECCO 2013; ASCO 2017

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Two Noval Approaches in ROC with Potential

Impact for First-line Treatment

• The use of PARP inhibitors

- Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) is a

key enzyme in the repair of DNA. Inhibition of PARP leads to

accumulation of breaks in DS-DNA and cell death.

- 30%-50% of HGSC may be susceptible to PARPi due to mutations in o

other HR repair genes in inhibition of BRCA function

• Immunotherapy, using immune checkpoint inhibitors (ICIs) - There are currently no approved immune therapies in ovarian cancer

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Randomized Trial of Maintenance Olaparib in Platinum-

sensitive High-Grade Serous Relapsed Ovarian Cancer

‘

Olaparib

400 mg po bid

Randomized 1:1

Placebo

po bid

Patients:

• Platinum-sensitive high-grade serous

ovarian cancer

• 2 previous platinum regimens

• Last chemotherapy was platinum-based

to which they had a maintained PR or

CR prior to enrolment

• Stable CA-125

Treatment

until

disease

Progression

Study aim and design

Primary end point : PFS

265 patients

Ledermann J, et al. N Engl J Med 2012;366:1382–92 17th ESO-E

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PFS in BRCA mutated patients

HR 0.18 (95% CI: 0.10-0.31)

Ledermann et al. Lancet Oncol. 2014;15(8):852–861

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Confirmatory Studies in Platinum-Sensitive

ROC with Germline BRCA Mutation

Study Drug formul. Pts Median PFS (HR)

• Ledermann Olaparib caps 136 11.2 vs 4.3 (0.18)

• Pujade Olaparib tabl 295 19.1 vs 5.5 (0.30)

• Coleman Rucaparib tabl 196 16.6 vs 5.4 (0.23)

• Mirza Niraparib caps 203 21.0 vs 5.5 (0.27)

Ledermann Lancet Oncol 2014; Pujade Lancet Oncol 2017; Coleman Lancet Oncol 2017; Mirza NEJM 2016

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Kap

Mirza MR et al. N Engl J Med 2016

Kaplan-Meier estimates of PFS

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Toxicity with Niraparib

• Most common grade 3 or 4 adverse events reported in the

niraparib group were:

- thrombocytopenia (33.8%)

- anemia (25.3%)

- neutropenia (19.6%)

• 14.7% of patients who received niraparib discontinued

because of an AE (vs 2.2% with placebo)

• No on treatment deaths. During FUP 3 patients died from

MDS or AML (1 in niraparib group, 2 in placebo group)

Mirza et al. N Engl J Med, 2016 17th ESO-E

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Olaparib

(N = 46)

Cediranib/olaparib

(N = 44)

P-value

BRCA mutation status

Carrier

Non-carrier

Unknown

24 (52.2%)

11 (23.9%)

11 (23.9%)

23 (52.3%)

12 (27.3%)

9 (20.5%)

0.92

Prior platinum-free interval

6-12 months

>12 months

26 (56.5%)

20 (43.5%)

23 (52.3%)

21 (47.7%)

0.83

Number of prior lines

1

2

3+

17 (37.0%)

18 (39.1%)

11 (23.9%)

26 (59.1%)

10 (22.7%)

8 (18.2%)

0.11

Randomized Trial of Olaparib ± Cediranib

in ‘Pt-sensitive’ relapsed ovarian cancer

Dx platinum-

sensitive

recurrent

ovarian cancer

Randomize 1:1

Cediranib

30mg daily +

Olaparib

capsules

200mg BID

Olaparib

capsules

400mg BID

Disease

progression by

RECIST v1.1

criteria

Presented by J. Liu (ASCO 2014; LBA #5500) and discussed by JA Ledermann

Published on-line in Lancet Oncology; September 10, 2014 17th ESO-E

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Combining Olaparib and Cediranib

• Increased overall response ( n=90)

– 47.8 % versus 79.6 % ( p=0.002)

• Improved progression-free survival

– Median PFS 9.0 versus 17.7 months ( HR 0.42;

95% CI -.23-0.76)

Presented by J. Liu (LBA abstract #5500) and discussed by JA Ledermann

Published on-line in Lancet Oncology: September 10, 2014 17th ESO-E

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Algorithm for selecting biological therapy in PS-ROC

2017

Trabectedin-PLD

If platinum is not an option

PFI > 6 months

BRCA?

Previous BEV 1L?

BEV 1L: YES

BRCA wt

Carbo Combo

BEV 1L: YES

BRCA mut

Carbo Combo

Olaparib maintenance

BEV 1L: NO

BRCA wt

Carbo-Gem-BEV Carbo-Pacli-BEV

BEV 1L: NO

BRCA mut

Carbo-Gem-BEV Carbo-Pacli-BEV

Carbo Combo

Olaparib maintenance

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Basis for Immune therapy – Immune Escape

Presented by: Tanguy Seiwert Melero I et al. Clin Cancer Res 2013;19:997-1008

• Expression of PD-L1

on

a) tumor cells &

b) macrophages

can suppress immune

surveillance.

• In mouse models

antibodies blocking

PD-1 / PD-L1

interaction lead to

tumor rejection

• Clinical prognosis

correlates with

presence of TILs and

PD-L1 expression in

multiple cancers.

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Drugs Interacting with PD-L1/PD1

Pathway in Ovarian Cancer*

Drug #Pts Previous lines Response %

Nivolumab 20 ≥ 4 in 55% 15

Pembrolizumab 26 ≥ 5 in 38.5% 11.5

Avelumab 124 ≥ 3 in 65.3% 9.7

Atezolizumab 12 ≥ 6 in 58% 25

Durvalumab 20 median 4 NR

*From Pujade-Lauraine, ESGO 2016 17th ESO-E

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Biological Agents integrated in

First-line Trials: Impact?

Study Trial Number Anti-A PARPi CPI Type

drug

Boost (AGO) NCT01462890 Bev 15 vs 30 mo

MGOG3005 NCT02470585 Veliparib 3 arm CT+V→M

PAOLA-1 NCT02477644 Bev Olaparib Olaparib M added

SOLO-1 NCT01844986 Olaparib Olaparib M (mBRCA)

PRIMA NCT02655016 Niraparib Niraparib M

JAVELIN100 NCT02718417 Ave Ave M, Ave+CT+M

IMAGYN50 NCT03038100 Bev Ate Ate M added to Bev

Ledermann JA. 11th Valencia Symposium, 2017 (Ann Oncol 2017; 28 (suppl 8): viii46-viii50

Bev= bevacizumab; Ave= avelumab; Ate= Atezolizumab; M= maintenance

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Incidence rates have fallen from between 1975 and 2013 from 16.3 to 11.4 per 100.000 and death rates from 9.8 to 7.2 per

100.000. (during 2004-2013 on average a fall of 1.9% vs 2.2% each year for incidence and mortality, respectively).

Presented by E.A. Eisenhauer at the Valencia meeting, March 3, 2017

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Take-Home Messages (1)

• Upfront surgery 6 x TC-based CT standard for ADOVCA

• NACT with IDS reasonable alternative for some patients

• Three-weekly paclitaxel/carboplatin (TC) still standard

• IPCT is standard in patients with optimally resected EOC

• Anti-angiogenic agents added to cytotoxic therapy in first

line may lead to survival benefit in far advanced disease

17th ESO-E

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Take-Home Messages (2)

• Anti-angiogenic (AA) drugs of benefit in patients with ROC : true for

bevacizumab, also for oral TKIs with AA proporties

• PARP inhibitors of benefit in patients with HGSC, in particular in

patients with BRCAm

• Combining olaparib and cediranib may herald beginning of treatments

that avoid cytotoxic chemotherapy in some OC pts

• Reactivation of immune surveillance by blocking PD1 interaction with

its ligands a promising approach for OC?

17th ESO-E

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DIAMOND

HARBOR

DESIGN

UZA

Thank you 17th ESO-E

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17th ESO-E

SMO Maste

rclass

Clin

ical O

ncology