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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?
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DIAMOND
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DESIGN
UZA
Thank you 17th ESO-E
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17th ESO-E
SMO Maste
rclass
Clin
ical O
ncology