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Recurrent disease
Eric Pujade-Lauraine
Hôtel-Dieu, Paris, France
What is standard?
4rd International Ovarian Cancer
Consensus Conference
Vancouver, June 25-27, 2010
5th Ovarian Cancer
Consensus Conference
Tokyo, November 7-9, 2015
Standard in recurrent disease
will not take into account
• Specific histology
• Frail patients: age, comorbidities, …
• Patient wish
News of the recurrence
• Patient opinion: « In some ways, news of the
recurrence was almost devastating than the
initial diagnosis. My hope of being cured was
shattered. I was terrified that the cancer was
back, and that it was the beginning of the
end »1
1-Ferrel B et al. Cancer 2003 98,5; 1061-71
Advanced Ovarian Cancer: A “chronic”
disease with multiple relapses
1°line
Platinum-sensitive
relpases
Platinum resistant
relapses
Chemotherapy
CA-125
Surgery
Occlusion
4 months
Symptoms
PFI: 12 months
PFI, platinum-free interval
8 months
A collapse of patient beliefs and
lifestyle
How to prevent recurrence ?
• positive attitude (82.5%),
• close medical follow-up (82.0%),
• vitamins or other supplements (82,0%)
• healthy lifestyle (69.0%),
• stress reduction (66.5%),
• diet (63.0%),
• and exercise (58.5%).
Stewart DE et al. Medscape 2001 oct
Listen to my hopes
I am hoping
1. Just for a less painful course of sickness
6%
2. For no recurrence of tumor-related symptoms
35%
3. To live longer than I otherwise would
24%
4. For complete healing without any
further complications
28%
Oskay-Özcelik G, et al. J Clin Oncol, 2013;31(Suppl): Abstract 5569.
Adjusting Hope With Reality
• Disparity of expectation and perceived
benefit from treatment is correlated
with scores of depression
Sjoquist KM, et al. Oncologist. 2013;18(11):1221-1228.
• Interventions to proactively reduce
patient stress, anxiety and/or
depression should be considered1
Should it be standard?
1-Lebel et al. J Cancer Surviv 2014 485-96
SURGERY
What is the role of cytoreductive
surgery for recurrent ovarian cancer?
4th Ovarian Cancer Consensus Conference
June 25 – 27, 2010
Vancouver, British Columbia , Canada
What is the role of cytoreductive
surgery for recurrent ovarian cancer?
• Surgery may be appropriate in selected patients.
• As yet, there is no level I evidence that demonstrates a survival
advantage associated with surgical cytoreduction for women with
recurrent ovarian cancer
• Cytoreductive surgery for women with recurrent ovarian cancer may be
beneficial if it results in optimal cytoreduction as defined in A5
(A5 = optimal resection defined as macroscopic complete resection)
•Randomized phase III trials evaluating the role of surgery in
recurrent ovarian cancer are a priority
4th Ovarian Cancer Consensus Conference
June 25 – 27, 2010
Vancouver, British Columbia , Canada
What is the role of cytoreductive
surgery for recurrent ovarian cancer?
1
0,9
0,8
survival probability
0,7 may be appropriate in selected
• Surgery
no residuals
median OS 45.2 mos.
patients.
0,6
• As yet, there is no level I evidence that demonstrates a survival
0,5
advantage associated with surgical cytoreduction for women with
0,4
recurrent ovarian cancer
0,3
residualscancer
> 10 mmmay be
• Cytoreductive
surgery for women with recurrent ovarian
0,2
beneficial
in A5
0,1 if it results in optimal cytoreduction as defined
residuals 1 - 10 mm
median OS
19.6 mos.
(A5 = optimal
resection defined as macroscopic complete
resection)
0
0
12
24
36
48
•Randomized phase III trials evaluating
the role of surgery in
months
Harter
P et al. Ann Surg Oncol 2006
DESKTOP
OVAR
I
recurrent ovarian cancer are a priority
Surgical trial in platinumsensitive relapse (1)
GOG 213
Intituive
patient
selection
Surgical trial in platinumsensitive relapse (2)
AGO-OVAR DESKSTOP III
Selection on AGO score
PS=0, 1st surgery residue =0, Ascite < 500cc
R
A
N
D
O
M
Cytoreductive
surgery
N=408
no surgery
platinum-based
chemotherapy
recommended
Primary
objective:
OS
March 2015 ACCRUAL COMPLETED!
CHEMOTHERAPY
4th Ovarian Cancer Consensus Conference
June 25–27, 2010
UBC Life Sciences Institute, Vancouver, BC
Recurrent Ovarian Cancer:
Population characteristics
Platinum-Free Interval
(Interval from last date of platinum dose until progression)
Expected
Platinum
Sensitivity
Progression while receiving last line of platinumbased therapy or within 1 month of last platinum dose
Refractory
1-6 months
Resistant
6-12 months
Partially sensitive
>12 months
Fully sensitive
1000
100
900
90
800
80
700
70
600
60
500
50
400
40
300
30
200
20
100
10
0-3 Prog 0-3 Non PD 3-12 mos 12-18 mos
Percentage
Days
Platinum-Free Interval and
Survival
18+ mos
PFS (days)
90
176
174
275
339
OS (days)
217
375
375
657
957
Response
(%)
9
24
35
52
62
Pujade-Lauraine, Proc ASCO #829, 2002
Recommended guidelines for
chemotherapy in relapse
Platinum
resistant
Partially Platinum
sensitive
Fully Platinum
sensitive
Platinum-free
interval <6 months
6-12 months
>12 months
Combination
chemotherapy:
Carboplatin
combination:
Platinum-based or
trabectedin-PLD
PLD, paclitaxel, ge
mcitabine
Non-platinum
single agent:
PLD, wkl
paclitaxel, gemcita
bine, topotecan
PLD: pegylated liposomal doxorubicin
Phase III Trials of Single Agent
Chemotherapy
PLD, Paclitaxel, Topotecan, Gemcitabine
Drug A
Drug B
N
TTP,
weeks
P
OS, weeks
P
Comment
Topotecan
Paclitaxel
226
23 vs 14
NS
61 vs 43
NS
50% Crossover
Paclitaxel
(bolus)
Paclitaxel
(weekly)
208
38 vs 26
NS
34 vs 59
NS
Less toxicity
with weekly
Oxaliplatin
Paclitaxel
86
12 vs 14
NS
42 vs 37
NS
74% platinum resistant
PLD
Topotecan
481
16 vs 17
NS
60 vs 57
NS
54% platinum resistant;
OS benefit in platinum
sensitive subgroup.
PLD
Paclitaxel
214
22 vs 22
NS
46 vs 56
NS
All patients
taxane-naïve
PLD
Gemcitabine
195
16 vs 13
NS
59 vs 55
NS
PLD
Gemcitabine
153
16 vs 20
NS
55 vs 50
NS
56% platinum resistant
Topotecan
Treosulfan
357
22 vs 12
.001
56 vs 48
.02
Second-line / third-line
therapy
PLD or
Topotecan
Canfosfamide
461
19 vs 9
<.01
59 vs 37
<.0001
ASSIST-1 trial
All third-line
TTP, time to progression; OS, overall survival, PLD: pegylated liposomal doxorubicin
Carboplatin-PLD versus
Carboplatin-paclitaxel (CALYPSO)
Median PFS,
mo
HR (95% CI)
CD
CP
11.3
9.4
0.82 (0.72, 0.94)
Carbo-PLD less toxic
than carbo-paclitaxel
PFS
Pujade-Lauraine E et al. J Clin Oncol 2010
1.00
Strategies to prolong PFI
1- Wait for symptoms
Proportion surviving
0.25
0.50
0.75
• Overall survival
Early
Delayed
Early (CA125 doubling)
vs Delayed
chemotherapy (at
symptom)
0.00
Median Time with
“good health score”
0
6
12 18 24 30 36 42 48 54 60
Months since randomisation
HR=1.00 (95%CI 0.82-1.22) p=0.98
Early
7.1 months
Delayed
9.2 months
p=0.15
Rustin GJ, et al. Lancet 2010
Standard for patients with
asymptomatic rise of CA125
• Observation
• Tamoxifen
Strategies to prolong
platinum-free interval
• Administer a non-platinum therapy
8 mos
5 mos
relapse
relapse
CARBOPLATINBASED Cx
Non-platinum
therapy
CARBOPLATINBASED Cx
Strategies to prolong
platinum-free interval
MITO 8
• Administer a non-platinum therapy
Recurrent
8 mos
5 mos
OC 6-12 mos
relapse
relapse
PLD 40 mg/m2
Q 28 d
R
CARBOPLATINBASED Cx
Non-platinum
therapy
Paclitaxel 175 mg/m2
CARBOPLATINCarboplatin
AUC = 5
BASED Cx
Q 21 d
Change to opposite
treatment after disease
progression
Strategies to prolong
platinum-free interval
MITO 8
• Administer a non-platinum therapy
Recurrent
8 mos
5 mos
OC 6-12 mos
relapse
relapse
PLD 40 mg/m2
Q 28 d
R
CARBOPLATINBASED Cx
Non-platinum
therapy
Paclitaxel 175 mg/m2
CARBOPLATINCarboplatin
AUC = 5
BASED Cx
Q 21 d
Change to opposite
treatment after disease
progression
PFI is not the only prognostic factor for PFS
in platinum-sensitive disease
Nomogram
Lee Cet al. Brit J Cancer 2011, 1-7
CHEMOTHERAPY
Lurbinectedin (PM01183) is a novel synthetic
entity, structurally related to trabectedin
Platinum Resistant
1.0
PM01183
Topotecan
Cumulative probability
0.9
(N=17 C=4)
(N
(N=16 C=2)
0.8
Lurbinectedin
0.7
0.6
HR: 0.30 p=0.005*
-
5.7 mo.
0.5
1.7
mo.
0.4
0.3
0.2
0.1
0.0
0
1
2
3
4
5
6
7
8
9
10
Time ( months)
months
Presented by:A. Poveda ASCO 2014
11
12
13
14
15
16
TARGETED THERAPY
Bevacizumab
VEGF
Bevacizumab
• Monoclonal antibody
• Binds VEGF-A
Platinum-sensitive relapse
1°line
chemotherapy
CA-125
Surgery
PFI: 12 months
PFI, platinum-free interval
Platinumsensitive
relapse
Platinum-sensitive relapse
1°line
chemotherapy
CA-125
Surgery
PFI: 12 months
PFI, platinum-free interval
Platinumsensitive
relapse
Carbo-Gem
Platinum-sensitive relapse
1°line
chemotherapy
CA-125
Surgery
PFI: 12 months
PFI, platinum-free interval
Platinumsensitive
relapse
Platinum-sensitive relapse
1°line
Platinumsensitive
relapse
chemotherapy
CA-125
Surgery
PFI: 12 months
PFI, platinum-free interval
8 months
Platinum-sensitive relapse
1°line
Platinumsensitive
relapse
chemotherapy
CA-125
Surgery
PFI: 12 months
PFI, platinum-free interval
8 months
Platinum-sensitive relapse
1°line
Platinumsensitive
relapse
chemotherapy
CA-125
Surgery
Bevacizumab, in combination with carboplatin and
gemcitabine, is indicated 8for
treatment of adult patients with
months
PFI: 12 months
first recurrence of platinum-sensitive epithelianovarian, fallopian-tube or primary peritoneal cancer who have
not received prior therapy with bevacizumab or other VEGF
PFI, platinum-free interval
inhibitors
or VEGF-receptor-targeted agents
Platinum-sensitive relapse
1°line
chemotherapy
CA-125
Surgery
BEVACIZUMAB
PFI: 12 months
PFI, platinum-free interval
Platinumsensitive
relapse
Platinum-sensitive relapse
1°line
chemotherapy
CA-125
Surgery
BEVACIZUMAB
PFI: 12 months
PFI, platinum-free interval
Platinumsensitive
relapse
Platinum-sensitive relapse
1°line
Platinumsensitive
relapse
chemotherapy
CA-125
Surgery
BEVACIZUMAB
Bevacizumab, in combination with carboplatin and
gemcitabine, is indicated for treatment of adult patients with
PFI: 12 months
first recurrence of platinum-sensitive epithelianovarian, fallopian-tube or primary peritoneal cancer who
have not received prior therapy with bevacizumab or
PFI, platinum-free
interval inhibitors or VEGF-receptor-targeted agents
other
VEGF
Platinum-resistant relapse
1°line
Platinumsensitive
relapse
Platinum resistant
relapse
Single agent
CA-125
Surgery
Bevacizumab in combination with paclitaxel, topotecan, or pegylated
liposomal doxorubicin is indicated for the treatment of adult patients
4 months
PFI: 12 months
with platinum-resistant recurrent epithelial ovarian, fallopian tube, or
primary peritoneal cancer who received no
twotwo
prior
nomore
morethan
than
prior
chemotherapy
regimens
and who
havehave
not not
received
prior
chemotherapy
regimens
and who
received
priortherapy
therapy
with
bevacizumab
or VEGF
inhibitor
or receptor–targeted
agents
with bevacizumab
or VEGF
inhibitors
or VEGF
receptor–targeted
agents
Limitations to Bevacizumab use
in relapse
• Prior treatment with Bev
• More than one prior line in platinum-sensitive
disease and more than 2 in resistant
• contraindications to BEV: uncontroled HTA,
renal or cardiac function impairment, recent
history of bleeding, thrombosis, wound
healing trouble, bowel/bladder wall
involvement
Is platinum-free interval predictive
of bevacizumab efficacy in
relapsing OC ?
Bevacizumab PFS efficacy in
different OC subsets
OCEANS3
AURELIA4
Tumor
size/stage
Platinumsensitive
relapse with
measurable
disease
Platinumresistant
relapse with
measurable
disease in
80%
Stratified
Hazard
Ratio
0.48
0.38
Absolute
benefit in
months
4.0
3.3
3. Aghajanian C, et al. J Clin Oncol. 2012;30(17):2039-2045. 4. Pujade-Lauraine E, et al. J Clin Oncol. 2014;32(13):1302-8
Bevacizumab PFS efficacy in
different OC subsets
ICON71
Low risk
group
Tumor
size/stage
Hazard
ratio
Absolute
benefit in
months
GOG2182
Complete
Stage III
surgical
with
resection +
macroscop
stage III
ic residue +
with residue
stage IV
<1 cm
ICON71
High risk
group
OCEANS3
AURELIA4
Stage III
with
residue
>1 cm +
stage IV
Platinumsensitive
relapse with
measurable
disease
Platinumresistant
relapse with
measurable
disease in
80%
0.87
0.72
0.67
0.48
0.38
<1
3.8
5.5
4.0
3.3
1. Perren TJ, et al. N Engl J Med. 2011;365(26):2484-2496. 2. Burger RA, et al. N Engl J Med. 2011;365(26):2473-2483. 3. Aghajanian C, et
al. J Clin Oncol. 2012;30(17):2039-2045. 4. Pujade-Lauraine E, et al. J Clin Oncol. 2014;32(13):1302-8.
Shall we wait for BEV
administration until the disease
get chemo- resistant?
QoL improvement in AURELIA
trial resistant disease
–5.7
(–10.7 to –
0.7)
–7.5
(–13.8 to –
1.2)
–5.2
(–13.4 to
2.9)
–7.3
(–16.9 to
2.3)
–6.4
(–11.6 to –
1.3)
Worsening
Chemo
(N=182)
Improvement
BEV + Chemo
(N=179)
Mixed Model
Repeated
Measures
analysis
(abdominal/GI
symptoms)
Clinical benefit in patients
with ascites (n=113)
Paracentesis in subgroup
with ascites
Primary hypothesis :
improvement in
abdominal/GI symptoms
(≥15%)
Patients (%)
Responders: 44.0% vs 4.1%
39.9% difference
[95% CI 23.9–55.9]).
Cycle number
Toxicity of interest during bevacizumab
treatment in first-line (GOG218 & ICON7 trials)
and in relapse (OCEANS & AURELIA trials)
Adverse event n (%)
GI events
Hypertension
GOG218
ICON7
2.6 a
3b
OCEANS AURELIA
2.4c
4.4d
22.9 (gr≥2) 18 (gr≥3) 17.4 (gr≥3) 20 (gr≥2)
Proteinuria (grade ≥3)
1.6
<1
8.5
1.7
Thromboembolic
evente
7.4
8
6.8
5.0
Bleeding (grade ≥3)
2.4
1
6.5
1.1
PRES
0.2
0
1
0.6
PRES = posterior reversible encephalopathy syndrome; gr : grade; aperforation, fistula, necrosis and leak grade≥2;bperforation,
fistula, abcess and wound-healing complications grade ≥3;c perforation, fistula and abcess all grades, wound-healing complications grade≥3;
d perforation and fistula/abcess grade ≥2; earterial any grade, venous grade ≥3
OS according to crossover to
BEV monotherapy in the CT arm
Chemotherapy
PD
BEV 15 mg/kg q3w
+ chemotherapy
PD
40%
BEV 15 mg/kg q3wb
(optional)
R
1:1
Investigator’s choice
(without BEV)
CT alone arm
Median OS, months
(95% CI)
No switch
to BEV
monotherapy
(N=110)
Switch
to BEV
monotherap
y (N=72)
BEV-CT arm
(n=179)
11.3
(7.5–13.3)
17.2
(15.0–20.2)
16.6
(13.7–19.0)
Unsolved questions
 Reuse of BEV in relapse after
prior BEV treatment?
 Best cytotoxic drug to combine
with BEV?
Bevacizumab use in platinumsensitive relapse after Bev: MITO16MANGO ov2
Carboplatin combo
PREVIOUS BEVACIZUMAB
Carboplatin combo
+ BEVACIZUMAB
OCEANS versus CALYPSO + BEV
regimen:Platinum-sensitive AGOOVAR 2.21 trial
platinumsensitive
PREVIOUS ANTI-ANGIOGENIC AGENT (yes vs no)
Bevacizumab with carboplatinpaclitaxel in platinum-sensitive
relapse: GOG-0213
PACLITAX
EL
PACLITAX
+EL
BEVACIZUMAB
+ BEVACIZUMAB
BEV efficacy in resistant patients
PFS
Chemo
PFS
BEV + chemo
Topotecan
2.1
5.8
PLD
3.5
5.4
Paclitaxel
3.9
10.4
(weekly)
Poveda A et al. ESMO 2012
BEV efficacy in resistant patients
PFS
Chemo
PFS
BEV + chemo
OS
Chemo
OS
BEV + chemo
Topotecan
2.1
5.8
13.3
13.8
PLD
3.5
5.4
14.1
13.7
Paclitaxel
3.9
10.4
13.2
22.4
(weekly)
Poveda A et al. ESMO 2012
Conclusion
• Bevacizumab is an active drug in recurrent
OC
• Efficacy is not linked to platinum-free
interval which makes BEV attractive for
the treatment of resistant disease,
particularly when symptomatic (ascites)
• The best single cytotoxic drug/combination
as BEV companion is under investigation
• Criteria which could select patients who
could benefit of Avastin reuse are eagerly
Active anti-angiogenic drugs
in recurrent ovarian cancer
Antiangiogenic Setting
drug
Pazopanib
resistant
Trebananib < 12 months
Fostrabulin
Cediranib
resistant
Design
HR
(95%CI)
Targets
wkl paclitaxel
+ pazopanib
VEGFR;
PDGFR; c-kit;
(0.25-0.69)
FGFR
wkl paclitaxel
+ pazopanib
0.66
Angio1 &2
(0.57–0.77)
Bevacizumab
+ fostrabulin
0.42
0.67
Chemo + concurrent and
0.57
sensitive
maintenance cediranib (0.44–0.74)
Vascular
disrupting
agent
VEGFR;
PDGFR;
FGFR
Olaparib
Anti-PARP
olaparib
• oral poly (ADP-ribose)
polymerase inhibitor
Study 19: Aim and design
•
Randomised, double-blind, placebo-controlled Phase II
study
Platinum-sensitive
high-grade serous
ovarian cancer
> 6 months
Platinum based
chemotherapy
relapse
Maintenance
Oral Olaparib
<8 weeks
Platinum
based
chemotherapy
R
400 mg/bd
1:1
Treatment until
disease progression
Placebo
bd
Ledermann J et al. N Engl J Med 2012;366:1382–92
Study 19: Summary of endpoints
in the BRCAm population
40
1.
0
0.
9
0.
8
0.
7
0.
6
0.
5
0.
4
0.
3
0.
2
0.
1
0
35
Proportion of patients
progression-free
+3 m
30
34.9
+8,6 m
25
20
+9,4 m
Olaparib BRCAm
15
Placebo BRCAm
+6,9 m
10
0
3
6
9
12
Time from randomisation (months)
BRCAm (n=136)
Events: total pts (%)
Median PFS, months
Olaparib
Placebo
26:74 (35.1)
46:62 (74.2)
11.2
4.3
HR=0.18
95% CI: 0.11, 0.31;
p<0.00001
15
15.6
31.9
23.8
15.2
11.2
5
4.3
6.2
0
initial
Baseline
relapse PFS1 Treatment
Traitement
traitement
PFS1
Treatment
rechute1
rechute
Relapse1 Relapse
2
suivante
(PFS2)
(PFS2)
OS
Overall
Survival
APPROVAL
“Monotherapy
adult
for the maintenance treatment of
patients with platinum-sensitive relapsed
BRCA-mutated
(germline
and/or
somatic)
high-grade serous epithelial ovarian, fallopian
tube, or primary peritoneal cancer who are in
response (complete response or partial response) to
platinum-based chemotherapy”.
Olaparib for BRCAm
high grade serous OC only?
Frequency of germline BRCA mutation
Total
population
Serous
Endometrioid
Clear
Cell
Mucinous
Alsop et al
14.1%
16.6%
8.4%
6.3%
NA
Risch HA et al
13.2%
18.0%
5.8%
5.4%
5.4%
9.1%
0%
Jacobi CE et al
13.9%
10.8%
0%
0%
0%
Malander S et al
8%
7.6%
13.0%
12.5%
0%
Soegaard M et al
7.1%
0%
Alsop K, et al. J Clin Oncol 2012;30(21):2654‒2663.; Risch HA, et al. J Natl Cancer Inst 2006;98(3):1694‒1706. Soegaard
M, et al. Clin Cancer Rev. 2008;14(12):3761-3767. Jacobi CE, et al. Genet Med 2007;9(3):173‒179; Malander S, et al. Eur J
Cancer. 2004;40(3):422-428. Pennington KP et al Clin Cancer Res. 2014 February 1; 20(3): 764–775
Olaparib for BRCAm only?
Platinum sensitivity
and NonBRCA HRm
genes
Proportion of patients
progression-free
Olaparib and
BRCA wt
No
of
patients
Platinum
sensitivi
ty
BRCAm
(somatic & germline)
67
85%
Non-BRCA
HRm genes
18
78%
No HRm
158
60%
Mutation (m) in
Homologous
recombination (HR)
genes
Olaparib BRCAwt
Placebo BRCAwt
0
3
6
9
12
Time from randomisation (months)
BRCAwt (n=118)
Olaparib
Placebo
Events: total pts (%)
32:57 (56.1)
44:61 (72.1)
Median PFS, months
5.6
5.5
15
HR=0.53
95% CI: 0.33, 0.84; p=0.007
Ledermann J et al. J Clin Oncol
2013;31(15S):abst 5505
Pennington KP et al. Clin Cancer Res
2015;20(3) 764
(%)
Is platinum-free interval predictive
of bevacizumab efficacy in
relapsing OC ?
Correlation Between Olaparib Response
and Prior Platinum Sensitivity and BRCA
mutation status
Germline BRCA
Status
BRCA mutation
positive1
BRCA mutation
negative2
Response to
Prior Platinum
RECIST Response to
Olaparib
Platinum
sensitive
6/13 (46%)
Platinum
resistant
8/24 (33%)
Platinum
sensitive
10/20 (50%)
Platinum
resistant
1/26 (4%)
1. Fong PC, et al. J Clin Oncol. 2010;28(15):2512-2519. 2. Gelmon KA, et al. Lancet Oncol. 2011;12(9):852-861.
Olaparib Trial in Heavily
Pretreated Ovarian Cancer
• n = 137 pts with measurable disease,
gBRCA+, and treated with at least 3 lines
of prior therapy
• Response rate: 34% (26-42) with a median
response duration of 7.9 months
• Conditional approval by FDA
Kaufman B et al. J Clin Oncol. 2015;33(3):244-50.
CONDITIONAL APPROVAL
Lynparza is indicated as monotherapy in patients with
deleterious germline BRCA mutated (as detected
by an FDA-approved test) advanced ovarian cancer
with 3 or more prior lines of chemotherapy
Heterogeneity of drug label
according to the continents
Drug/indication
EU
Japan
BEV first line
X
X
BEV platinum-sensitive
X
X
X
X
BEV platinum-resistant
US
X
OLAPARIB platinum-sensitive
OLAPARIB multiple lines
X
X
And heterogeneity of
reimbursement!
Guideline for recurrent OC
MODULATION
FROM
STANDARD
FRAILTY
HISTOLOGY
Platinumfree interval
Asymptomatic
CA125 increase
•follow-up or Tam
PATIENT
WISH
GEOGRAPHY
Label-Reimbursement
Prior
Bevacizumab
Number of
prior lines
PLATINUM-SENSITIVE
PFI>6 months
BRCAm
Multiple lines (>3)
•Best of care or
olaparib (BRCAm, US)
PLATINUM-RESITANT
PFI<6 months
• Carboplatin-gemcitabine-bevacizumab
(1st PS relapse, no prior BEV)
• Platin-based chemo followed by
olaparib maintenance (BRCAm)
• Bevacizumab with wkl paclitaxel
or PLD, topotecan
(1st or 2nd relapse, no prior BEV)
•
• Carboplatin combination or nonplatinum combination (PFI 6-12,..)
• Single non-platinum agent drug
• BACK UP slides
A Randomized Phase 2 Trial
of Olaparib and Cediranib vs Olaparib
Alone
in Recurrent Platinum-sensitive Ovarian
Olaparib
Cancer capsules
Dx platinumsensitive
recurrent
ovarian cancer
400mg BID
Disease
progression by
RECIST v1.1
criteria
Randomize 1:1
Cediranib
30mg daily +
Olaparib
capsules
200mg BID
PFS events
Median
PFS
NonHematologic
Adverse
Event
Olaparib
Ced/Ola
(N = 46)
(N = 44)
Hypertension
-
18 (41)
Grade 3/4
Olaparib
Ced/Olap
28
19
Diarrhea
-
10 (23)
9.0 mo
17.7 mo
Fatigue
5 (11)
12 (27)
Nausea
-
2 (5)
p=0.005
HR 0.42 (95% CI: 0.23-0.76)
Headache
- Liu ASCO 22014
(5)
Presented by: Joyce