The document discusses the use of PARP inhibitors in the treatment and maintenance of epithelial ovarian cancer, highlighting their effectiveness in prolonging progression-free survival (PFS). It details various studies, including SOLO-1 and others, showing significant benefits of PARP inhibitors like olaparib and niraparib in patients with BRCA mutations and those with high-grade serous ovarian cancer. The challenges of recurrent disease and the importance of tailored maintenance strategies are also addressed.

1. PARPi in Ovarian Cancer:
Turnaround in journey of
epithelial ovarian cancer
Chandan Das
Medical Oncology
PGIMER, Chandigarh

2. OVERVIEW
PARP & PARPi
Frontline Maintenance
PSR maintenance
PARPi in treatment

3. 3
a mPFS values measured from beginning of chemotherapy (ie, day of randomization) to the first disease progression and, thereafter, from one progression to the subsequent
one or to death.
L, line; mPFS, median progression-free survival; PFS, progression-free survival.
Hanker LC, et al. Ann Oncol. 2012;23(10):2605-12.
mPFS
10.2 mo
(95% CI: 9.6–10.7)
mPFS
6.4 mo
(95% CI:
5.9–7.0)
mPFS
5.6 mo
(95% CI:
4.8–6.2)
mPFS
4.4 mo
(95% CI:
3.7–4.9)
mPFS
4.1 mo
(95% CI:
3.0–5.1)
mPFS
18.2 mo
(95% CI: 17.3–19.1)
5L 6L
4L
3L
2L
1L
Fourth
Recurrence
Fifth
Recurrence
Third
Recurrence
Second
Recurrence
First
Recurrence
Note: Data depict historical
mPFS of watch-and-wait,
and do not represent PFS
observed with
maintenance treatment.
The Unmet Need
~80%
Median PFS decreases after every recurrence:

4. How to prevent/Delay Relapse ?
 Pazopanib
 2 month PFS benefit
 Hypertension
 Bleeding
 Hypothyroidism
 Hepatotoxic
 Bevacizumab
 4 month PFS benefit
 Hypertension
 Bleed
 Perforation
 Proteinuria
 Ideal Maintenance
 Effective
 Safe
 Specific

5. gBRCA and sBRCA mutation in Ca Ovary
5
Approximately
40%
of patients with BRCAm OC may have no
relevant family history2,3
Approximately
20%
of OC patients a gBRCAm1,
while an additional
5-9%
may have a sBRCAm2
1. Alsop K, et al. J Clin Oncol 2012; 30:2654-63 2. Pal T, et al. Cancer 2005; 104:2807-16 3. Vergote I, et al. Eur J Cancer 2016; 69:127-34 4. Kwong A, et al. Asia-Pac J Clin Oncol, 2019; 1-12; 4. Susana Beatriz Goncalves, et al.
Journal of Clinical Oncology 2019 37:15_suppl, e17050-e17050
The use of family history, age and histology type alone for patient selection in BRCAm testing would miss a
significant proportion of cases.4 Offering gBRCA test may also miss significant sBRCAm population.
Approximately
29%
of OC patients
Harbour
tBRCAm

6. Targeting DNA repair Defect

7. PARP

8. PARPi

9. PARPi in frontline maintenance Ca Ovary

10. SOLO-1Olaparib in first line Ca Ovary Maintenance

11. SOLO1 5 year PFS
Olaparib
(N=260)
Placebo
(N=131)
118 (45) 100 (76)
56.0 13.8
42.2
HR 0.33 (95% CI 0.25–0.43)
Events, n(%)
Median PFS,months
Difference, months
Median treatmentduration:
Olaparib, 24.6months
Placebo†
, 13.9months
Patientsfreefromdisease
progressionanddeath(%)
Placebo
Olaparib
51%
88%
35%
74%
27%
60%
22%
52%
21%
48%
2-year
treatment cap*100
90
80
70
60
50
40
30
20
10
0
0 6 12 18 24 30 36 42 48 54 60 66 72 78
Months sincerandomization
No. at risk
Olaparib 260 229 212 194 173 140 129 115 101 91 58 30 2 0
Placebo 131 103 65 53 41 38 30 24 23 22 16 3 0

12. SOLO 1
Subgroup
Analysis

13. n(%)
Olaparib
(n=260)
Placebo
(n=130)
AnyAE 256 (98) 120 (92)
Grade ≥3AE 103 (40) 25 (19)
Serious AE 55 (21) 17 (13)
AE leading to dose interruption 136 (52) 22 (17)
AE leading to dose reduction 75 (29) 4 (3)
AE leading to treatment discontinuation 30 (12) 4 (3)
MDS/AML 3 (1) 0 (0)
New primarymalignancy 7 (3) 5 (4)
No additional cases of MDS/AML reported;
incidence remained <1.5%
Follow-up for MDS/AML continued until death due to anycause
Overall Patients in CR at baseline
PFS2
Olaparib
(n=260)
Placebo
(n=131)
Olaparib
(n=189)
Placebo
(n=101)
Events, n(%) 80 (31) 61 (47) 49 (26) 45 (45)
Event free at 5years,
%
64 41 68 44
Median,months NR 42.1 NR 52.9
HR 0.46
(95% CI 0.33–0.65)
HR 0.48
(95% CI 0.32–0.71)
TSST
Events, n(%) 95 (37) 77 (59) 64 (34) 56 (55)
Event free at 5years,
%
62 36 65 39
Median,months NR 40.7 NR 47.7
HR 0.46
(95% CI 0.34–0.63)
HR 0.50
(95% CI 0.35–0.72)
SOLO1: Secondary efficacy outcomes

14. PAOLA 1 Trial
OLAPARIB

15. PAOLA 1:PFS

16. VELIA/GOG-3005Veliparib +Carboplatin/Paclitaxel
 Primary endpoint: PFS in Arm 1 vs Arm 3 with hierarchical testing in BRCA
mutation positive, HRD positive, and whole population
Patients with newly diagnosed
high-grade serous ovarian
cancer, FIGO Stage III or IV,
ECOG PS 0-2, and no CNS
metastases
(N = 1140)
Carboplatin + Paclitaxel +
Veliparib 150 mg BID
(n = 382)
Carboplatin + Paclitaxel +
Placebo
(n = 375)
Carboplatin + Paclitaxel +
Veliparib 150 mg BID
(n = 383)
Coleman. ESMO 2019. Abstr LBA3.
Veliparib 400 mg BID
Placebo
Placebo
Combination CT: Cycles 1-6 Maintenance: Cycles 7-36
Carboplatin AUC 6 Q3W + paclitaxel 80 mg/m2 QW or 175 mg/m2 Q3W.
Stratification by stage, region, type of
cytoreduction, residual disease, CT regimen,
gBRCA status*
*Germline BRCA mutation status added as stratification factor ~ 14 mos after trial initiation due to noted imbalance.

17. VELIA/GOG-3005: PFS for Patients With BRCA
Mutations
CT + Veliparib  Veliparib CT + Placebo  Placebo
Events, n/N (%) 34/108 (31.5) 51/92 (55.4)
Median PFS, mos (95%
CI) 34.7 (31.8-NR) 22.0 (17.8-29.1)
Slide credit: clinicaloptions.comColeman. ESMO 2019. Abstr LBA3. Reproduced with permission.
0
20
40
60
80
100
PFS(%)
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44
108
92
102
90
99
89
97
88
95
84
90
80
88
74
82
63
80
57
76
50
73
46
65
38
53
29
45
24
38
19
30
13
21
6
14
4
9
2
5
0
1 1 0
Veliparib
throughout
Control
HR: 0.44 (95% CI: 0.28-0.68; P < .001)
Mos From Randomization
Combination Maintenance
Patients at Risk, n

18. VELIA/GOG-3005: PFS for Patients With
HRD (Including BRCA Mutations)
CT + Veliparib  Veliparib CT + Placebo  Placebo
Events, n/N (%) 87/214 (40.7) 124/207 (59.9)
Median PFS, mos
(95% CI) 31.9 (25.8-38.0) 20.5 (17.8-22.8)
Coleman. ESMO 2019. Abstr LBA3. Reproduced with permission.
0
20
40
60
80
100
PFS(%)
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44
214
207
203
199
195
196
191
191
182
183
167
170
161
158
150
134
140
119
130
104
121
97
109
79
82
55
72
47
58
34
44
22
30
11
19
9
14
4
5
2
1
0
1 0
HR: 0.57 (95% CI: 0.43-0.76; P < .001)
Mos From Randomization
Combination Maintenance
Veliparib
throughout
Control
Patients at Risk, n

19. VELIA/GOG-3005: PFS in ITT Patient
Population (Regardless of HRD or BRCA
Mutation Status)
Slide credit: clinicaloptions.com
CT + Veliparib  Veliparib CT + Placebo  Placebo
Events, n/N (%) 191/382 (50.0) 237/375 (63.2)
Median PFS, mos (95%
CI) 23.5 (19.3-26.3) 17.3 (15.1-19.1)
Coleman. ESMO 2019. Abstr LBA3. Reproduced with permission.
0
20
40
60
80
100
PFS(%)
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44
382
375
352
356
337
340
329
328
308
297
275
260
253
236
228
202
208
172
192
153
172
143
153
119
111
84
95
70
76
55
55
36
38
21
26
16
19
10
7
3
2
0
1 0
HR: 0.68 (95% CI: 0.56-0.83; P < .001)
Mos From Randomization
Combination Maintenance
Veliparib
throughout
Control
Patients at Risk, n

20. Maintenance Niraparib After Initial
Therapy for Ovarian Cancer (PRIMA):
Phase III Study Design
 Double-blind, randomized, placebo-controlled phase III trial
 Primary endpoint: PFS by BICR
 Hierarchical testing in patients with HRD (HR benefit: 0.5) followed by the overall patient population
(HR benefit: 0.65)
 Key secondary endpoint: OS; other secondary endpoints: PFS2, TFST, patient-reported
outcomes, safety
Patients with newly diagnosed
advanced ovarian cancer with CR or PR
following first-line platinum-based CT;
high-grade serous or endometroid
pathology; stage III with residual
disease, stage IV, or inoperable
(N = 730)
Niraparib 200-300* mg QD
(n = 484)
Placebo
(n =244)
Stratification by 1L platinum CT,
CR/PR to 1L therapy, HRD status
Tx for 36 mos or
until PD
*Initiated treatment with 300 mg QD for patients ≥ 77
kg and with platelets ≥ 150,000/μL, 200 mg QD for
patients < 77 kg and/or with platelets < 150,000/μL.
González-Martin. ESMO 2019. Abstr LBA1.

21. PRIMA: PFS in HRD and Overall Patient
Populations (Primary Endpoint)
PFS in HRD Population PFS in Overall Patient Population
HR: 0.43 (95% CI: 0.31-0.59; P < .001)
Median PFS, Mos
21.9
10.4
Niraparib
Placebo
HR: 0.62 (95% CI: 0.50-0.76; P < .001)
Median PFS, Mos
13.8
8.2
Niraparib
Placebo
100
80
60
40
20
0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Mos Since Randomization
PFS(%)
Pts at Risk, n
Niraparib
Placebo
247
126
231
117
215
99
189
79
184
70
168
57
111
34
76
21
66
21
42
11
22
5
19
5
13
4
4
1
0
0
*
** ** * ***
* *** ** ******** ** ******** ** ******* *****
* * **** * ***** * **
100
80
60
40
20
0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Mos Since Randomization
PFS(%)
Pts at Risk, n
Niraparib
Placebo
487
246
454
226
385
177
312
133
295
117
253
90
167
60
111
32
94
29
58
17
29
6
21
6
13
4
4
1
0
0
*** ** **
**
**** **
******
****
*
**
**** *
*
*
***
* *** *
****
** **** ** ** ** ***** ** ******* * ***** * **

22. Frontline maintenance Options

23. PARPi in Second line maintenance Ca Ovary

24. Platinum sensitive relapse

25. Phase II Study 19 of Olaparib Maintenance in
Platinum-Sensitive Recurrent Ovarian Cancer
 Primary endpoint: PFS (RECIST 1.0)
 Secondary endpoints: OS, safety, tolerability
 Exploratory endpoints: time to first subsequent therapy or death, time to
second subsequent therapy or death
Patients with platinum-sensitive,
recurrent high-grade serous
ovarian cancer; ≥ 2 prior
platinum-based regimens with
CR/PR to most recent platinum-
based therapy; stable CA-125
(N = 265)
Treatment until
disease
progression
Olaparib
400 mg BID PO
(n = 136)
Placebo
BID PO
(n = 129)
Ledermann. NEJM. 2012;366:1382.

26. Study 19 :PFS
Ledermann. NEJM. 2012;366:1382.
HR: 0.35 (95% CI: 0.25-0.49; P < .001)
Treatment
Number of Patients
With Event (%)
Median PFS,
Mos
Olaparib 60 (44.1) 8.4
Placebo 93(72.1) 4.8
Olaparib
Placebo
Mos
150 3 6 9 12
1.0
0.8
0.6
0.4
0.2
0
ProbabilityofPFS
Patients at Risk, n
Olaparib
Placebo
136
129
104
72
51
23
23
7
6
1
0
0

27. Study 19:OS

28. Study 19:Exploratory endpoints in BRCAm

29. “
”
SOLO2: Final OS Analysis of
Maintenance Olaparib in Platinum-
Sensitive, Relapsed Ovarian Cancer
with BRCA Mutation

30. SOLO2 Trial design

31. Baseline characteristics
Characteristic
Olaparib
(n = 196)
Placebo
(n = 99)
Primary tumor location, %
 Ovary
 Fallopian tube/primary
peritoneal
 Other/Missing
83
16
2
87
13
0
Histology, %
 Serous
 Endometrioid
 Mixed/Missing
93
5
2
87
8
5
gBRCA mutation by Myriad testing,
%
 BRCA1
 BRCA2
67
30
62
35
ECOG PS 0/1, % 83/16 78/22
Characteristic
Olaparib
(n = 196)
Placebo
(n = 99)
Prior platinum response, %
 Complete
 Partial
46
54
47
53
# prior platinum regimens, %
 2
 3
 4
 ≥ 5
56
31
9
4
63
20
12
5
Platinum-free interval, %
 > 6-12 months
 > 12 months
40
60
40
60
Prior bevacizumab, % 17 20
> 2 cm target lesions at BL, % 15 18

32. SOLO2: Investigator-Assessed PFS
Pujade-Lauraine. Lancet Oncol. 2017;1274.
100
80
60
40
20
0
PFS(%)
Mos
Olaparib
Placebo
HR: 0.30 (95% CI: 0.22-0.41; P <
.0001)
Patients at Risk, n
Olaparib
Placebo
196
99
182
70
156
37
134
22
118
18
104
17
89
14
82
12
32
7
29
6
3
0
2
0
0
0
360 3 6 9 12 15 18 21 24 27 30 33

33. Olaparib for the maintenance treatment of PSR OC1-3
Phase III study3
Recurrent BRCAm ovarian cancer after two prior lines of
platinum therapy (n=295)
Maintenance in patients achieving a CR/PR on
platinum therapy
Olaparib tablets PO 300mg BID
Olaparib significantly prolonged PFS compared with placebo
(HR 0.30; 95% CI 0.22 to 0.41; p<0.0001)
Study 19
Phase II study1,2
Recurrent ovarian cancer after two or more prior lines of
platinum therapy (n=265)
Maintenance in patients achieving a CR/PR on
platinum therapy
Olaparib capsules PO 400mg BID
Olaparib significantly prolonged PFS compared with placebo
(HR 0.35; 95% CI 0.25 to 0.49; p<0.00001)
Trend towards benefit for overall survival (HR of 0.73; 95% CI
0.55 to 0.95; nominal p=0.025; statistical significance not reached)
Improvements in PFS and OS were also seen in the non-BRCAm
subgroup (HR 0.54 [95% CI 0.34 to 0.85], p=0·0075; and HR 0.83
[95% CI 0.55 to 1.24], nominal P=0.37; respectively)
BID=twice daily; BRCAm=BRCA1/2 mutation; CI=confidence interval; CR=complete response; HR=hazard ratio; non-BRCAm=no mutations in BRCA1/2; OC=ovarian cancer; OS=overall survival;
PFS=progression-free survival; PO=orally; PR=partial response; PSR=platinum-sensitive relapsed
1. Ledermann J, et al. N Engl J Med. 2012;366(15):1382–1392; 2. Ledermann J, et al. Lancet Oncol. 2016;17(11):1579–1589; 3. Pujade-Lauraine et al. Lancet Oncol. 2017;18(9):1274–1284

34. Final OS analysis
OS Adjusted for subsequent PARP inhibitor use
(in 38% placebo, 10% olaparib pts)
Olaparib
(n = 196)
Placebo
(n = 99)
Events, n (%) 116 (59) 65 (66)
Median OS, mos 51.7 38.8
HR (95% CI) 0.75 (0.54-1.00); P = .0537
Olaparib
(n = 196)
Placebo
(n = 99)
Events, n (%) 116 (59) 61 (62)
Median OS, mos 51.7 35.4
HR (95% CI) 0.56 (0.35-0.97)100
90
80
70
60
50
40
30
20
10
0
Overallsurvival(%)
Mos
780 6 12 18 24 30 36 42 48 54 60 66 72
No.at
risk
Olaparib
Placebo
196
99
192
99
187
93
172
79
145
66
130
57
120
50
105
42
98
38
86
33
77
31
39
16
7
0
0
0
42
%
33
%
Olaparib
Placebo
100
90
80
70
60
50
40
30
20
10
0
Overallsurvival(%)
Mos
780 6 12 18 24 30 36 42 48 54 60 66 72
No.at risk
Olaparib
Placebo
Placebo adjusted
196
99
99
192
99
99
187
93
92
172
79
75
145
66
60
130
57
50
120
50
46
105
42
34
98
38
0
86
33
0
77
31
0
39
16
0
7
0
0
0
0
0
Place
Placebo, adjusted

35. SOLO2: Time to Subsequent Therapy and
Duration of Treatment Exposure
Time to Subsequent Therapy
Olaparib
(n = 196)
Placebo
(n = 99)
Events, n (%) 139 (71) 86 (87)
Median TFST, mos 27.4 7.2
HR (95% CI) 0.37 (0.28-0.48); P < .0001
Duration of Treatment Exposure
100
90
80
70
60
50
40
30
20
10
0
Patientsevent-free(%)
Months since randomization
780 6 12 18 24 30 36 42 48 54 60 66 72
28
%
13
%
Olaparib
Placebo
Olaparib
(n = 195)
Placebo
(n = 99)
≥ 1
years
≥ 2
years
≥ 3
years
≥ 4
years
≥ 5
years
Patientsexposedtotreatment(%)
10
090
80
70
60
50
40
30
20
10
0
62
21
45
13
31
12
27
9
22
9
Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 6002-6002.

36. Final Safety Analysis
Safety outcome
Olaparib (n = 195) Placebo (n = 99)
Primary Final Primary Final
Mean total treatment duration, mos 17.4 29.1 9.0 13.1
Any TEAE, %
 Grade ≥ 3
 Serious
98
37
18
99
46
26
95
18
8
95
19
8
TEAE leading to:
 Dose interruption, %
 Dose reduction, %
 Discontinuation, %
45
25
11
50
28
17
18
3
2
19
3
3
MDS/AML, %
 During safety follow-up (TEAE)
2 8
4
4 4
0
Pneumonitis, % 2 2 0 0

37. MDS/AML Risk

38. SOLO2: Treatment-Emergent Adverse Events
Poveda. ASCO 2020. Abstr 6002. Reproduced with permission.
All grades
Grade ≥ 3
100 80 60 40 20 0 0 20 40 60 80 100
TEAEs (%)
Olaparib (N = 195)
29.1 months
Placebo (N = 99)
13.1 months
Mean total treatment duration
Nausea
Fatigue or asthenia
Anemia
Vomiting
Diarrhea
Abdominal pain
Headache
Constipation
Neutropenia
Decreased appetite
Cough
Dysgeusia
Dizziness
Back pain
Arthralgia
Thrombocytopenia
Hypomagnesemia
Dyspepsia
35
392
102
201
20
313
3
6
14
23
4
11
6
6
6
142
14
41
10
9
76 3
67 6
2146
40
28
34
3
1
3
126
23
24
24 7
1
19 1
19
17 1
16
16
216
115
15

39. SOLO 2 Conclusions
14m
PFS
improved
20m
TSST
improved
17m
OS
improved

40. “
”
Health-related Quality of Life and Patient-
Centred Outcomes With Olaparib Maintenance
After Chemotherapy in Patients With Platinum-
Sensitive, Relapsed Ovarian Cancer and a
BRCA1/2 Mutation (SOLO2/ENGOT Ov-21): A
Placebo-Controlled, Phase 3 Randomized Trial
MICHAEL FRIEDLANDER 1, VAL GEBSKI 2, EMMA GIBBS 2, LUCY DAVIES 3, RALPH BLOOMFIELD 4, FELIX HILPERT 5, LARI B WENZEL 6, DANIEL EEK 7, MANUEL
RODRIGUES 8, ANDREW CLAMP 9, RICHARD T PENSON 10, DIANE PROVENCHER 11, JACOB KORACH 12, TOMASZ HUZARSKI 13, LAURA VIDAL 14, VANDA
SALUTARI 15, CLARE SCOTT 16, MARIA ORNELLA NICOLETTO 17, KENJI TAMURA 18, DAVID ESPINOZA 2, FLORENCE JOLY 19, ERIC PUJADE-LAURAINE

41. Trial Outcome Index Score

42. SOLO2: Quality-Adjusted PFS
Olaparib
(n = 185)
Placebo
(n = 94)
Difference
(95% CI)
P Value
Mean PFS, mos 17.55 8.94 8.61
(6.47 to 10.87)
< .0001
Mean utility (mixed model) 0.80 0.81 -0.02
(-0.05 to 0.02)
.284
QAPFS, mos 13.96 7.28 6.68
(4.98 to 8.54)
< .0001

43. SOLO2: Time Without Symptoms of Disease or Toxicity
• TWiST duration
significantly
longer with
olaparib vs
placebo
Duration, Mos Olapari
b
(n =
185)
Placeb
o
(n = 94)
Differen
ce
(95% CI)
P Value
TWiST 13.5 7.21 6.29
(2.95-
8.58)
< .0001
Toxicity 3.69 0.71 2.98
(1.52-
4.68)
.0002

44. NOVA : Niraparib in PSR Ovary

45. March 30 - April 2, 2014
Sheraton Sonoma County
Petaluma, California
Treatment
PFS
Median
(95% CI)
(Months)
Hazard Ratio
(95% CI)
p-value
% of Patients
without
Progression or
Death
12 mo 18 mo
Niraparib
(N=138)
21.0
(12.9, NE) 0.27
(0.173, 0.410)
p<0.0001
62% 50%
Placebo
(N=65)
5.5
(3.8, 7.2)
16% 16%
Mirza MR et al. N Engl J Med 2016; Presidential Symposium, ESMO 2016
ENGOT-OV16 / NOVA:PFS:gBRCA+

46. BRCAwt
Treatment
PFS
Median
(95% CI)
(Months)
Hazard
Ratio
(95% CI)
p-value
% of Patients
without
Progression
or Death
12 mo 18 mo
Niraparib
(N=71)
9.3
(5.8, 15.4) 0.38
(0.231,
0.628)
p=0.0001
45% 27%
Placebo
(N=44)
3.7
(3.3, 5.6)
11% 6%
Treatment
PFS
Median
(95% CI)
(Months)
Hazard
Ratio
(95% CI)
p-value
% of Patients
without
Progression
or Death
12 mo 18 mo
Niraparib
(N=35)
20.9
(9.7, NR) 0.27
(0.081,
0.903)
p=0.0248
62% 52%
Placebo
(N=12)
11.0
(2.0, NR)
19% 19%
sBRCAmut
Treatment
PFS
Median
(95% CI)
(Months)
Hazard
Ratio
(95% CI)
p-value
% of Patients
without
Progression or
Death
12 mo 18 mo
Niraparib
(N=92)
6.9
(5.6, 9.6) 0.58
(0.361,
0.922)
p=0.0226
27% 19%
Placebo
(N=42)
3.8
(3.7, 5.6)
7% 7%
HRD-positive HRD-negative
Mirza MR et al. N Engl J Med 2016; Presidential Symposium, ESMO 2016
ENGOT-OV16 / NOVA:PFS in Non-Germline BRCA mutant

47. *CR (defined by RECIST v1.1) or PR (defined by RECIST v1.1 and/or a GCIG CA-125 response [CA-125 within normal range]) maintained until entry to ARIEL3 (≤8 weeks of last dose of
chemotherapy). †ATM, ATR, ATRX, BARD1, BLM, BRIP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, MRE11A, NBN, PALB2, RAD50,
RAD51, RAD51B, RAD51C, RAD51D, RAD52, RAD54L, RPA1.
ARIEL3: Rucaparib in Relapsed Ca Ovary
• HRR status by NGS mutation analysis
 BRCA1 or BRCA2
 Non-BRCA HRR gene†
 None of the above
• Response to recent platinum
 CR
 PR
• Progression-free interval after
penultimate platinum
 6 to <12 months
 ≥12 months
Patient eligibility Stratification
• High-grade serous or endometrioid
epithelial OC, primary peritoneal, or
fallopian tube cancers
• Sensitive to penultimate platinum
• Responding to most recent platinum
(CR or PR)*
 Excludes patients without assessable
disease following second surgery
• CA-125 within normal range
• No restriction on size of residual tumour
• ECOG PS ≤1
• No prior PARP inhibitors
Placebo
BID
n=189
Rucaparib
600 mg BID
n=375
Randomisation2:1
5
0

48. ARIEL 3: PFS

49. Selecting the Best PARPi Maintenance

50. PARPi in treatment

51. Study 42: Olaparib Monotherapy

52. SOLO 3 : Olaparib vs non platinum therapy in PSR
Ovary

53. SOLO 3: Efficacy

54. SOLO 3: PFS ITT Polulation

55. Study 10 /2a: Rucaparib Mono therapy

56. QUADRA: Niraparib for HRD+Ca Ovary

57. Future of PARPi

58. Future of PARPi

59. OReO Study: Olaparib Retreatment in
Platinum-Sensitive Ovarian Cancer

60. MEDIOLA

61. Turnaround time for Ca Ovary with PARPi
PFS TSST OS QOL
Acceptable
AE

62. Holy Grails of Ovarian Cancer
Complete
Cytoreductive
Surgery
Platinum
Sensitivity
PARP
Inhibition