Ignace Vergote MD PhD FACS FSPS Chairman Leuven Cancer Institute and Dept Obamp Gyn Leuven European Union Ovarian Carcinoma Classical Evolution of the disease Symptoms Late Diagnosis ID: 780498
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Slide1
Behandeling van het recidief ovariumcarcinoom
Ignace Vergote MD PhD FACS FSPS
Chairman, Leuven Cancer
Institute
and
Dept
Ob&
Gyn
, Leuven
, European Union
Slide2Ovarian Carcinoma:
Classical Evolution of the disease
Symptoms
(Late) Diagnosis
Chemotherapy
Primary Debulking
Interval
Debulking
Platin-
sensitive
Platin-
resistant
Supportive
Care
Death
Maintenance
CR or PR
Progression
> 6
mnths
Progression
< 6
mnths
Maintenance
Secondary
Debulking
Tertiary
Debulking
Slide3OS 3,126
pts
. / 1,837
events
PFS 3,126
pts
. / 2,375
events
months
5.0%
progressing
during
chemotherapy
17.2% PFS 0-6 months
46,2% PFS
12-60 months
8.6 % PFS
60-120 months
22.8% PFS 6-12 months
Randomisation
Results
of
the
AGO-OVAR
metadatabase
(
du Bois et al
, Cancer 2009)
PFS and OS after start of 1st line chemotherapy
Slide4Treatment
goals
:
Resistant
(0-6
months
)
Sensitive
(6-12
months
)
Sensitive
(12+
months
)
Symptom relief
(Response)
Control
stable disease
(SD)
Delay
PD, PFS
OS
prolongation
…
Cure
…
…not
now
…
Goals of
treatment
in
recurrent
ovarian
cancer
are
different
according
to
platin
sensitivity
!!!
Outcome 1st surgery
PFS, progression-free survival
Slide5Vergote I , et al 2010, National Oncological Guidelines - Belgium www.collegeoncologie.be/files/files/Ovarian_Cancer_V1.2010
_(
EN).pdfOvarian cancer recurrence
Treatment Algorithm
Slide6ENGOT Ov-20 / AGO-OVAR OP.4 / DESKTOP III
Role of surgery in
platin-sensitive relapsed ovarian cancer
Stratification
:
- Platinum-
free
-
interval
6-12 vs
> 12 months- 1st
line platinumbased
chx: yes
vs no
RANDO
Mcytoreductivesurgery
platinum-based
chemotherapy*recommended* Recommended platinum-based
chemotherapy regimens: - carboplatin/paclitaxel carboplatin/gemcitabine
carboplatin/peg liposomal
doxorubicin or other platinum combinations in prospective
trials no
surgery
Accrual: 232/408
Platin-sensitive
first
relapse
Positive DESKTOP score
:
No
ascites (< 500
mL
)
Complete
resection at primary
surgery- ECOG 0
Slide7Prognostic
factors for Survival
after secondary debulking
(Adapted from
Hauspy
and
Covens
,
Curr Opinion Oncology 2007
)AIOM 2000
Slide8Meta-analysis Zang et al
Br J Cancer 2011 (n = 1100)
Low risk : Score 0 – 2:
median
OS : 63
months
( n = 418)
High risk : Score 3 – 8 :
median
OS: 19 months (n = 682)
Slide9Secondary
Debulking Surgery
Besides the AGO score (ECOG, no ascites and no residual tumor after first surgery
), time to relapse and spread of the disease
should
be
considered when selecting
patients for secondary debulking surgery.
Whole body diffusion-weighted MRI (and if
not available PET-CT or laparoscopy) have an
added value to CT.
Slide10Ovarian Carcinoma:
Evolution since 2010: targeted therapy
Symptoms
(Late) Diagnosis
Chemotherapy
Primary Debulking
Interval
Debulking
Platin-
sensitive
Platin-
resistant
Supportive
Care
Death
Maintenance
CR or PR
Progression
> 6
mnths
Progression
< 6
mnths
Maintenance
Bevacizumab: GOG218, ICON7
Nintedanib
: AGO OVAR12
Pazopanib: AGO OVAR16
VEGF
Bev: OCEANS
Cediranib
: ICON6
ANG
Trebananib: ENGOT-ov2
PARP
Olaparib: PARP19
Bev: AURELIA
Trebananib: Trinova-1
Secondary
Debulking
Tertiary
Debulking
Slide11Phase III studies in
ovarian cancer with
targeted drugs
First line
Platin-
sensitive
Pl-resist
GOG218
BevICON7Bev
AGOPazoOCEANSBevICON6Ced
PARP*OlaAURELIABevPFS *
3.81.75.64.0
3.14.03.3PFS HR0.720.81
0.770.840.570.350.48OS
0.40.9NA- 1.82.72.03.3OS HR
0.91(NS)**NS0.99 (NS)1.03(NS)
0.700.88(NS)0.85(NS)* :
difference in months; **NS: Not Significant; Significant unless stated NS; *** Phase
II ≠
≠≠Burger NEJM 2011; Perren NEJM 2011 – Oza ECC 2013 for OS; du Bois ASCO 2013;
Aghajanian JCO 2012;Ledermann ECC 2013; Ledermann ASCO 2013; Pujade-Laurraine ASCO 2012 - Witteveen ECC 2013
Slide12Phase III studies in
ovarian cancer with
targeted drugs
First line
Platin-
sensitive
Pl-resist
GOG218
BevICON7Bev
AGOPazoOCEANSBevICON6
CedPARP***OlaAURELIABevPFS **
3.81.75.64.0
3.14.03.3PFS HR0.720.81
0.770.840.570.350.48OS
0.40.9NA- 1.82.72.03.3OS HR
0.91(NS)***NS0.99 (NS)1.03
(NS)0.700.88(NS)0.85(NS)≠
≠Burger NEJM 2011; Perren NEJM 2011 (PFS) – Oza ECC 2013 (OS); du Bois ASCO 2013; Aghajanian
JCO 2012; Ledermann ECC 2013; Ledermann ASCO 2013; Pujade-Laurraine ASCO 2012 (PFS)- Witteveen ECC 2013 (OS)
* :
difference in months
; **NS: Not Significant; Significant unless stated NS; *** Phase II
Slide13Phase III studies in
ovarian cancer with
targeted drugs
First line
Platin-
sensitive
(> 6
mnths PFI)
0-12 monthsPl-resist
GOG218BevICON7BevAGOPazo
OCEANSBevICON6CedPARP***
OlaTrinova-1 TreAURELIABev
PFS **3.81.75.64.03.1
4.01.83.3PFS HR0.72
0.810.770.840.570.350.660.48
OS0.40.9NA
- 1.82.72.01.73.3OS HR0.91
(NS)***NS0.99 (NS)1.03(NS)0.700.88(NS)
0.86(NS)0.85(NS)
≠≠Burger NEJM 2011; Perren NEJM 2011 – Oza ECC 2013 for OS; du Bois ASCO 2013;
Aghajanian JCO 2012;Ledermann ECC 2013; Ledermann ASCO 2013; Pujade-Laurraine ASCO 2012 - Witteveen ECC 2013; Monk ECC 2013
* :
difference in months; **NS:
Not Significant; Significant unless stated NS;
*** Phase II
Slide14Why
is the OS only
significant with
cediranib
in ICON 6?
Carbo
Carbo-Gem
Carbo-Gem
Carbo-Gem
+ Bev
PFS
5.88.6
8.412.4
OS17.3
18
35.233.3
AGO-Ovar 2.5OCEANS
Pfisterer JCO 2006;
Aghajanian
JCO 2012
Slide15Comparison
first recurrence platin sensitive ovarian
cancer
Pfisterer JCO 2006;
Aghajanian
JCO 2012
Slide16How
to explain the OS
difference with
cediranib
in ICON 6?
Carbo
Carbo-Gem
Carbo-Gem
Carbo-Gem
+ Bev
Carbo
Comb
CarboComb
+ CedMaint
PFS5.8
8.68.4
12.48.7
11.1 OS
17.3
1835.233.3
20.326.3AGO-Ovar
2.5OCEANS
Pfisterer JCO 2006;
Aghajanian
JCO 2012
; Ledermann, ICON6, ECC 2013 LBA 10
ICON6
Slide17Targeted
therapy in ovarian cancer
What we know
:New anti-angiogenetic
drugs,
both
VEGF and Angiopoetin
targeting drugs are active in prolonging PFS of ovarian cancer.
PARP inhibition is very interesting in high-grade
serous ovarian cancer and especially in BRCA patients.Current
ongoing studies on targeted therapy base the targeted therapy on
genetic profile of the tumor (often linked to
the histological type). OVARIAN CANCER = MANY DISEASES!
Slide18Targeted
therapy in ovarian cancer
What we do not
know:When should
an
angiogenese inhibitor
be
given (first-line, platin-sensitive, platin-resistant)? Or should we give them in all
lines?Which angiogenesis inhibitor should be
prefered in which group of ovarian cancer patients
? Biomarkers for efficacy of antiangiogenesis are still
needed. Potential for combination of VEGF inhibitors
with other classes of antiangiogenetic drugs (e.g. ang inhibitors) or other targeted
therapy such as e.g. PARP inhibitors.