The PAOLA-1 trial found that for patients with newly diagnosed advanced ovarian cancer, maintenance olaparib + bevacizumab led to improved overall survival compared to placebo + bevacizumab in the subgroup of patients with HRD-positive tumors. At 5 years, the overall survival rate was 65.5% for olaparib + bevacizumab versus 48.4% for placebo + bevacizumab in this subgroup. No new safety concerns were observed. The trial provides support for adding olaparib to first-line treatment with bevacizumab for patients with HRD-positive advanced ovarian cancer.

1. PAOLA-1 Phase III Trial: Final
Overall Survival Results of Maintenance
Olaparib + Bevacizumab in Patients With
Newly Diagnosed Advanced Ovarian Cancer
Supported by educational grants from AstraZeneca; Bristol Myers Squibb;
Exelixis, Inc.; Gilead Sciences, Inc.; and Merck Sharp & Dohme Corp.
CCO Independent Conference Coverage*
of the ESMO 2022 Annual Congress; September 9-13, 2022; Paris, France
*CCO is an independent medical education company that provides state-of-the-art medical information to
healthcare professionals through conference coverage and other educational programs.

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Slide credit: clinicaloptions.com

3. Slide credit: clinicaloptions.com
PAOLA-1: Background
 PAOLA-1/ENGOT-ov25 phase III trial1
‒ Examined efficacy and safety of maintenance olaparib + bevacizumab vs placebo +
bevacizumab in patients with newly diagnosed advanced ovarian cancer who had
received first-line SoC treatment including bevacizumab
‒ Significant PFS benefit observed with olaparib + bevacizumab vs placebo +
bevacizumab
‒ Overall: HR: 0.59 (95% CI: 0.49-0.72; P <.001)
‒ In patients with HRD-positive tumors: HR: 0.33 (95% CI: 0.25-0.45)
 Current final analysis sought to assess any OS advantage at 5 yr of olaparib +
bevacizumab vs placebo + bevacizumab based on observed PFS advantage in
primary analysis2
1. Ray-Coquard. NEJM. 2019;381:2416. 2. Ray-Coquard. ESMO 2022.

4. Slide credit: clinicaloptions.com
PAOLA-1: Study Design
Ray-Coquard. ESMO 2022. Abstr LBA29.
 Randomized, placebo-controlled phase III trial for patients with newly diagnosed FIGO stage III-IV,
high-grade serous/endometrioid ovarian, fallopian tube, or primary peritoneal cancer
 Primary endpoint: investigator-assessed PFS per RECIST v1.1
 Key secondary endpoints: PFS2, OS (planned for 3 yr after the primary PFS analysis or
60% data maturity)
Olaparib 300 mg BID for 2 yr +
Bevacizumab 15 mg/kg on Day 1 Q3W for 15 mo*
(n = 537)
Placebo for 2 yr +
Bevacizumab 15 mg/kg on Day 1 Q3W for 15 mo*
(n = 269)
2:1
Patients with newly diagnosed
ovarian cancer and PR or CR after
upfront or interval surgery, standard
platinum/taxane-based CT, and
≥3 cycles of bevacizumab
(N = 806)
*Including during CT.

5. Slide credit: clinicaloptions.com
PAOLA-1: Baseline Characteristics
Ray-Coquard. ESMO 2022. Abstr LBA29.
Characteristic
Olaparib + Bev
(n = 537)
Placebo + Bev
(n = 269)
Median age, yr (range) 61 (32-87) 60 (26-85)
FIGO stage, n (%)
 III
 IV
378 (70)
159 (30)
186 (69)
83 (31)
HRD status,* n (%)
 HRD positive
 tBRCAm
 HRD positive excluding
tBRCAm
 HRD negative/HRD unknown
 HRD negative
255 (47)
157 (29)
97 (18)
282 (53)
192 (36)
132 (49)
80 (30)
55 (20)
137 (51)
85 (32)
Characteristic, n (%)
Olaparib +
Bev (n = 535)
Placebo + Bev
(n = 269)
History of cytoreductive surgery
Upfront surgery
• No residual macroscopic disease
• Residual macroscopic disease
Interval cytoreductive surgery
• No residual macroscopic disease
• Residual macroscopic disease
No surgery
271 (50)
160 (59)
111 (41)
228 (42)
163 (71)
65 (29)
38 (7)
138 (51)
85 (62)
53 (38)
110 (41)
75 (68)
35 (32)
21 (8)
Response after surgery/PBC
 NED
 CR
 PR
290 (54)
106 (20)
141 (26)
141 (52)
53 (20)
75 (28)
*BRCA status confirmed by central labs and HRD status by Myriad myChoice HRD
plus; patients in tBRCAm and HRD-positive excluding tBRCAm subgroups do not equal
total number of patients in HRD-positive subgroups due to differences in testing
methods.

6. Slide credit: clinicaloptions.com
PAOLA-1: OS (ITT Population)
 19.7% and 45.7% of patients
in olaparib + Bev and
placebo + Bev arms,
respectively, received
PARP inhibitor during any
subsequent treatment
 Median time from first cycle
of chemotherapy to
randomization: 6 mo
Ray-Coquard. ESMO 2022. Abstr LBA29. Reproduced with permission.
Olaparib + Bev
(n = 537)
Placebo + Bev
(n = 269)
Events,* n (%) 288 (53.6) 158 (58.7)
Median OS, mo 56.5 51.6
5-yr OS rate, % 47.3 41.5
HR: 0.92 (95% CI: 0.76-1.12; P = .4118)
*55% maturity.
Time From Randomization (Mo)
OS
(%)
100
80
60
40
20
0
0 12 24 36 48 60 72 80
5-yr OS rate
47.3%
41.5%
Olaparib + bevacizumab
Placebo + bevacizumab
Patients at Risk, n
Olaparib + bevacizumab
Placebo + bevacizumab
537
269
530
267
528
264
517
261
503
250
480
242
463
229
440
220
420
208
398
199
376
188
357
179
347
166
329
160
308
154
295
146
286
139
276
132
262
121
217
96
169
76
113
51
82
37
40
20
19
5
4
2
0
0

7. Slide credit: clinicaloptions.com
PAOLA-1: OS in HRD-Positive Subgroup
 17.3% and 50.8% of patients
in olaparib + Bev and
placebo + Bev arms,
respectively, received
PARP inhibitor during any
subsequent treatment
Ray-Coquard. ESMO 2022. Abstr LBA29. Reproduced with permission.
Olaparib + Bev
(n = 255)
Placebo + Bev
(n = 132)
Events, n (%) 93 (36.5) 69 (52.3)
Median OS, mo 75.2* 57.3
5-yr OS rate, % 65.5 48.4
HR: 0.62 (95% CI: 0.45-0.85)
*Median unstable; <50% data maturity.
Time From Randomization (Mo)
OS
(%)
100
80
60
40
0
0 12 24 36 48 60 72 80
5-yr OS rate
65.5%
48.4%
Olaparib + bevacizumab
Placebo + bevacizumab
Patients at Risk, n
Olaparib + bevacizumab
Placebo + bevacizumab
255
132
253
130
253
129
252
128
252
126
244
121
238
117
231
114
225
109
215
105
205
100
200
96
195
91
189
89
183
86
176
82
174
79
170
77
164
70
142
59
116
44
83
29
62
21
32
9
17
2
4
1
0
0
20

8. Slide credit: clinicaloptions.com
PAOLA-1: PFS in HRD-Positive Subgroup
Ray-Coquard. ESMO 2022. Abstr LBA29. Reproduced with permission.
Olaparib + Bev
(n = 255)
Placebo + Bev
(n = 132)
Events, n (%) 136 (53.3) 104 (78.8)
Median PFS, mo 46.8 17.6
5-yr PFS rate, % 46.1 19.2
HR: 0.41 (95% CI: 0.32-0.54)
Time From Randomization (Mo)
PFS
(%)
Olaparib or placebo for up to 2 yrs
100
80
60
40
0
0 12 24 36 48 60 72 80
5-yr PFS rate
19.2%
46.1%
Olaparib + bevacizumab
Placebo + bevacizumab
Patients at Risk, n
Olaparib + bevacizumab
Placebo + bevacizumab
255
132
252
129
242
118
236
103
223
91
214
79
194
62
183
52
165
41
162
37
147
34
143
30
138
29
127
25
123
24
119
24
117
21
112
20
103
19
79
15
63
13
40
8
31
6
8
2
5
0
3 0
20

9. Slide credit: clinicaloptions.com
Time From Randomization (Mo)
0 12 24 36 48 60 72 80
PAOLA-1: OS by HRD Status
Ray-Coquard. ESMO 2022. Abstr LBA29. Reproduced with permission.
Olaparib +
Bev
(n = 157)
Placebo +
Bev
(n = 80)
Events, n (%) 48 (30.6) 37 (46.3)
Median OS, mo 75.2† 66.9
5-yr OS rate, % 73.2 53.8
Subsequent PARPi, n (%) 38 (24.2) 44 (55.0)
HR: 0.60 (95% CI: 0.39-0.93)
Olaparib +
Bev
(n = 97)
Placebo +
Bev
(n = 55)
Events, n (%) 44 (45.4) 32 (58.2)
Median OS, mo NR 52.0
5-yr OS rate, % 54.7 44.2
Subsequent PARPi, n (%) 9 (9.3) 23 (41.8)
HR: 0.71 (95% CI: 0.45-1.13)
*By central labs. †Median unstable; <50% data maturity. ‡By Myriad myChoice HRD Plus.
Olaparib +
Bev
(n = 192)
Placebo +
Bev
(n = 85)
Events, n (%) 140 (72.9) 58 (68.2)
Median OS, mo 36.8 40.4
5-yr OS rate, % 25.7 32.3
Subsequent PARPi, n (%) 46 (24.0) 34 (40.0)
HR: 1.19 (95% CI: 0.88-1.63)
BRCAm* HRD Positive Excluding BRCAm†
HRD Negative‡
Time From Randomization (Mo)
OS
(%)
100
80
60
40
0
20
157
80
155
76
146
68
130
59
117
54
80
33
11
3
0
0
Olaparib + bevacizumab
Placebo + bevacizumab
5-yr OS rate
53.8%
73.2%
0 12 24 36 48 60 72 80
100
80
60
40
0
20
97
55
96
54
81
44
66
37
58
29
37
15
5
0
0
5-yr OS rate
44.2%
54.7%
Patients at Risk, n
Olaparib + bevacizumab
Placebo + bevacizumab
Time From Randomization (Mo)
0 12 24 36 48 60 72 80
100
80
60
40
0
20
192
85
169
76
126
60
97
46
66
35
30
17
1
2
0
5-yr OS rate
32.3%
25.7%

10. Slide credit: clinicaloptions.com
PAOLA-1: AEs of Special Interest in Final OS Analysis
Ray-Coquard. ESMO 2022. Abstr LBA29.
AEs, n (%)
Olaparib + Bev
(n = 535)
Placebo + Bev
(n = 267)
Olaparib + Bev
(n = 535)
Placebo + Bev
(n = 267)
Olaparib + Bev
(n = 535)
Placebo + Bev
(n = 267)
MDS/AML/AA 6 (1.1) 1 (0.4) 7 (1.3) 4 (1.5) 9 (1.7) 6 (2.2)
New primary malignancies* 7 (1.3) 3 (1.1) 13 (2.4) 5 (1.9) 22 (4.1) 8 (3.0)
Pneumonitis/ILD/bronchiolitis† 6 (1.1) 0 (0.0) 6 (1.1) 0 (0.0) 7 (1.3) 2 (0.7)
*New primary malignancies: olaparib arm: plasma cell myeloma (n = 1), basal cell carcinoma (n = 1), breast cancer (n = 11), bronchial carcinoma
(n = 1), colon cancer (n = 1), glioblastoma (n = 1), malignant neoplasm (n = 1), pancreatic carcinoma (n = 1), squamous cell carcinoma (n = 2), and
ureteric cancer (n = 1); placebo arm: papillary thyroid cancer (n = 1), breast cancer (n = 4), diffuse large B-cell lymphoma (n = 1), malignant lung
neoplasm (n = 1), and malignant neoplasm (n = 1).
†Pneumonitis/ILD/bronchiolitis events: olaparib arm: bronchiolitis (n = 1), pneumonia (n = 1), acute respiratory distress syndrome (n = 1),
interstitial lung disease (n = 2), and pneumonitis (n = 2); placebo arm: coronavirus infection (n = 1) and pneumonitis case (n = 1).
Primary PFS Analysis
(DCO: March 22, 2019)
Primary PFS2 Analysis
(DCO: March 22, 2020)
Primary OS Analysis
(DCO: March 22, 2022)

11. Slide credit: clinicaloptions.com
PAOLA-1: Investigators’ Conclusions
 Clinically meaningful OS benefit observed in HRD-positive patients with newly diagnosed advanced
ovarian cancer treated with maintenance olaparib + bevacizumab vs placebo + bevacizumab1
‒ 5-yr OS rate: 65.5% vs 48.4%; HR: 0.62 (95% CI: 0.45-0.85)
‒ Observed even with 50% of patients in control arm receiving PARP inhibitor post progression
‒ Benefit observed regardless of BRCAm status
 Similar OS observed in HRD-negative subgroup of each treatment arm1
 No new safety signals compared with earlier reports of this trial2
‒ Incidences of MDS/AML and new primary malignancies remain low and similar between arms
 Investigators concluded that these data support addition of olaparib to bevacizumab as SoC for
HRD-positive patients with newly diagnosed advanced ovarian cancer1
‒ Confirms that treatment outcomes can be optimized and should be guided by biomarker testing
1. Ray-Coquard. ESMO 2022. Abstr LBA29. 2. Ray-Coquard. NEJM. 2019;381:2416.

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