Redefining Ovarian Cancer Treatment

Amr Shafik

Professor of Clinical Oncology

Ain Shams University

Cairo, Egypt

​

Disclosure

• This is a Non-Promotional GSK Symposium.
• This presentation doesn’t contain any promotional claims
• No part of this presentation can be copied, retrieved, photographed or downloaded without permission from GSK and the speaker.
• Speaker is not an employee of GSK
• There are no completed direct head-to-head-trials of these products. These data are from different clinical trials, and since there are inherent limitations in cross-study comparisons, caution should be exercised in interpreting these data. These data are for information purposes only and are not intended to imply or infer the noninferiority or superiority of either product, in terms of efficacy or safety.
• The clinical cases discussed represents the opinion of the expert  

​

​

Disclaimer and COI:

Incidence and Mortality of Ovarian Cancer in Egypt

Globocan 2022

Globocan 2022 https://gco.iarc.who.int/media/globocan/factsheets/populations/818-egypt-fact-sheet.pdf (last accessed December 2024)

4

EPIDEMIOLOGY

Different pathways exist to repair damaged DNA in normal cells

DSB = double-strand breaks; SSB = single-strand break. Jones P, et al. J Med Chem. 2015;58:3302-3314.

8

Double-strand breaks (DSB)

Single-strand breaks (SSB)

Homologous recombination (HR)

High accuracy

Non-homologous end joining (NHEJ)

Error prone

Mismatch repair (MMR)

Nucleotide excision repair (NER)

Base excision repair (BER)

Unrepaired SSBs in dividing

cells can lead to DSBs

DNA damage

FOR REACTIVE USE ONLY

Repair mechanisms

PRINCIPLES

Half of high-grade serous OCs are HRd and exhibit a high degree of genomic instability

BRIP1, BRCA1 interacting helicase 1; HR = homologous recombination; HRD = homologous recombination deficiency; HRd = homologous recombination deficient; gBRCAm = germline breast cancer gene mutation; OC = ovarian cancer; tBRCAm = tumor BRCA mutation.

1. Abkevich V, et al. Br J Cancer. 2012;107:1776-1782; 2. The Cancer Genome Atlas Research Network. Nature. 2011;474:609-615; 3. Konstantinopoulos PA, et al. Cancer Discov. 2015;5:1137-1154.

42

All ovarian

(50% HRd + 50% HRp)

HRd

tBRCAm

gBRCAm

15%

(germline)

25%

(somatic/germline)

50%

HRd

BRCA1/2 and RAD51 promoter methylation, BRIP1, and other genes involved in HR^1,2

25% are tBRCAm

at diagnosis^1,2

15% are gBRCAm

at diagnosis¹⁻³

FOR REACTIVE USE ONLY

• Although BRCA1/2 mutations may be the primary drivers of HRD in OC, other mechanisms are thought to play a role¹

50% of OCs are HRd including BRCAm,

PRINCIPLES

Advances in 1L OC management have improved SoC for patients

1LM = first-line maintenance; BRCAm = BRCA mutant; OC = ovarian cancer; OS = overall survival; PARPi = poly(ADP-ribose)polymerase inhibitor; PFS = progression-free survival; SoC = standard of care.

1. Lheureux S, et al. CA A Cancer J Clin. 2019;69:280–304. 2. Tewari KS, et al. J Clin Oncol. 2019;37:2317–2328. 3. Oza AM, et al. Lancet Oncol. 2015;16:928–936. 4. Kristensen G, et al. J Clin Oncol. 2011;18(Suppl):LBA5006 http://www.icon7trial.org/media/1049/icon7-asco-v12-final-

2011_06_04.pdf (Accessed: Jan 2024). 5. Randall L, et al. presented at SGO 2013, 7–12 Mar, Los Angeles, CA. 6. Moore K, et al. N Engl J Med. 2018;379:2495–2505. 7. González-Martín A, et al. N Engl J Med. 2019;381:2391–2402. 8. Li N, et al. JAMA Oncol 2023:9:1230–1237.

9. Ray-Coquard I, et al. N Engl J Med. 2019;381:2416–2428. 10. DiSilvestro P, et al. J Clin Oncol. 2023;41:609–617. 11. Banerjee S, et al. Lancet Oncol. 2021;22:1721−1731. 12. González-Martín A, et al. Eur J Cancer. 2023;189:112908. 13. Lorusso D, et al. presented at ESMO Gyn 2023, 23–24 Feb, Barcelona, Spain. 14. González-Martín A. at presented ESMO Gyn 2023; 23–24 Feb, Barcelona, Spain. 15. Hardesty MM, et al. Gynecol Oncol. 2022:166:219–229. 16. Konstantinopoulos PA, et al. JAMA Oncol. 2019;5:1141–1149.

17. Drew Y, et al. Ann Oncol. 2019:S0923–S07534. 18. Randall LM, et al. presented at ASCO 2022 (Poster 5573), 3–7 Jun, Chicago, IL. 19. Monk BJ, et al. Int J Gynecol Cancer. 2021;31:1589–1594. 20. Harter P, et al. presented at ASCO 2019 (TPS5598) 29–31 May (virtual).

20^th century

2023

Future

Surgery¹

Chemotherapy¹

Olaparib⁶

Olaparib +

bevacizumab⁹

Long-term outcomes from 1LM PARPi trials demonstrate improved PFS and OS in patients receiving PARPi^10–14

Novel combinations are currently under investigation^15–22

Novel biomarkers may help personalize treatments in advanced OC

Bevacizumab monotherapy 1LM trials demonstrated a PFS benefit in patients with advanced OC, as well as an OS benefit for certain higher-risk groups^4,5

​

Bevacizumab^2,3 Niraparib^7,8

5-year PFS data confirms the long-term benefit of olaparib + bevacizumab combination therapy, particularly in patients with BRCAm tumors

2010s

21. Coleman RL, et al. presented at SGO 2020 (Poster 182), 28–31 Mar, Toronto, Canada. 22. Hardy-Bessard AC, et al. presented at ASCO 2020 (TPS6101) 29–31 May (virtual).

DEVELOPMENTS

HR: 0.73

10.4 vs 13.9 mos

Median D: 3.5 mos

HR: 0.87

17.4vs 19.8 mos

Median D: 2.4 mos

Burger et al. N Engl J Med 2011 Perren T… Mirza MR et al. N Engl J Med 2011

GOG-218

ICON7

Antiangiogenic therapy Bevacizumab in First-Line

Note: In the absence of head-to-head data between PARPi efficacy and safety comparisons between PARPi are not to be made.

BEVACIZUMAB

PRIMA trial design

^aAt study start, all patients received a fixed starting dose of 300 mg once daily. Subsequently, the protocol was updated to use an individualized starting dose adjusted according to baseline body weight/platelet count.

1L = first-line; BICR = blinded independent central review; CA-125 = cancer antigen 125; CR = complete response; CT = chemotherapy; HR = homologous recombination; HRD = HR deficiency; HRd = HR deficient; HRnd = HR status not determined; HRp = HR proficient; NACT = neoadjuvant chemotherapy; OC = ovarian cancer; OS = overall survival; PCS = primary cytoreductive surgery; PD = progressive disease; PFS = progression-free survival; PFS2 = time to second progression or death; PR = partial response; PRO = patient-reported outcome; Pt = platinum; SD = stable disease; TFST = time to first subsequent therapy; VRD = visible residual disease.

González-Martín A, et al. N Engl J Med 2019;381:2391–402. Mirza MR, et al. presented at ASCO 2020, 29–31 May (virtual); https://clinicaltrials.gov/study/NCT02655016#participation-criteria (Accessed: September 2024)

PRIMA was a randomized, double-blind, placebo-controlled, Phase 3 trial of niraparib maintenance therapy in patients with newly diagnosed, advanced OC that have responded to 1L, platinum-based CT

​

• Patients with stage III disease who have had complete cytoreduction (i.e., no VRD) after PCS

​

• Patients with SD or PD on platinum therapy

Key exclusion criteria

R 2:1

Niraparib

Placebo

Patients with newly diagnosed OC at high risk of recurrence after response to 1L Pt-based CT

Patients treated once daily^a for 36 months or until disease progression

Primary endpoint: PFS by BICR Key secondary endpoint: OS Secondary endpoints:

PFS2, TFST, PRO, safety

Endpoint assessment

• High-grade serous or endometrioid pathology
• Stage III: PCS with visible residual disease post surgery, NACT with and without residual disease, or inoperable
• Stage IV: PCS regardless of residual disease, NACT or inoperable
• CR or PR following platinum first-line treatment per RECIST criteria
• CA-125 in the normal range or a ≥90% decrease in CA-125 during 1L treatment that was stable for at least 7 days
• Tissue for HRD testing was required at screening (Myriad myChoice^®)

Key inclusion criteria

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Niraparib PFS in the overall and HRd populations

Data cut-off date: 8 April 2024; median duration of follow-up: 6.2 years. Data are investigator-assessed PFS.

CI = confidence interval; HRD = homologous recombination deficiency; HRd = homologous recombination deficient; ITT = intention-to-treat; PFS = progression-free survival; yr = year. Monk BJ, et al. Ann Oncol 2024:S0923–7534(24)03762–1.

PFS in HRd

PFS in ITT

Niraparib (n=247)

Placebo (n=126)

Events, n (%)

150 (60.7)

105 (83.3)

Median PFS, months

24.5

11.2

Hazard ratio (95% CI)

0.51 (0.40–0.66)

Niraparib (N=487)

Placebo (N=246)

Events, n (%)

352 (72.3)

209 (85.0)

Median PFS, months

13.8

8.2

Hazard ratio (95% CI)

0.66 (0.55–0.78)

0

10

20

30

40

50

60

70

80

90

100

0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84

Months since randomization

Niraparib

Placebo

3-yr PFS rate: 29% vs 18%

4-yr PFS rate:

24% vs 13% 5-yr PFS rate:

22% vs 12%

Progression-free survival (%)

0

10

20

30

40

50

60

70

80

90

100

Niraparib

Placebo

0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84

Months since randomization

3-yr PFS rate:

^{43% vs 23%} 4-yr PFS rate:

38% vs 18%

5-yr PFS rate: 35% vs 16%

No. at risk

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The PFS of niraparib in the HRp population

Data cut-off date: 8 April 2024; median duration of follow-up: 6.2 years. Data are investigator-assessed PFS.

CI = confidence interval; HRp = homologous recombination proficient; PFS = progression-free survival; yr = year. Monk BJ, et al. Ann Oncol 2024:S0923–7534(24)03762–1.

Niraparib (n=169)

Placebo (n=80)

Events, n (%)

147 (87.0)

71 (88.8)

Median PFS, months

8.4

5.4

Hazard ratio (95% CI)

0.67 (0.50–0.89)

No. at risk Niraparib Placebo

Progression-free survival (%)

0

10

20

60

​

50

​

40

​

30

70

80

90

100

Niraparib

Placebo

3-yr PFS rate: 11% vs 10%

4-yr PFS rate:

9% vs 7%

5-yr PFS rate:

8% vs 7%

0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84

Months since randomization

169 128 87 56 44 31 27 23 19 16 16 14 12 11 11 9 7 7 4 0

80 53 26 19 17 11 9 7 7 7 7 6 5 5 4 4 4 4 3 1 1 0

PFS in HRp

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OS in the ITT and HRd populations

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Data cut-off date: 8 April 2024; median duration of follow-up: 6.2 years.

CI = confidence interval; HRd = homologous recombination deficient; ITT = intention-to-treat; OS = overall survival; yr = year. Monk BJ, et al. Ann Oncol 2024:S0923–7534(24)03762–1.

OS in ITT

OS in HRd

0

10

20

30

40

50

60

70

80

90

100

Niraparib

Placebo

3-yr OS rate: 74% vs 74%

4-yr OS rate:

^{61% vs 61%} 5-yr OS rate:

55% vs 56%

Overall survival (%)

0

10

20

30

40

50

60

70

80

90

100

Niraparib

Placebo

3-yr OS rate:

63% vs 64%

4-yr OS rate:

48% vs 51%

5-yr OS rate:

42% vs 44%

Hazard ratio (95% CI)

1.01 (0.84–1.23)

Niraparib

(n=247)

Placebo

(n=126)

Events, n (%)

120 (48.6)

65 (51.6)

Median OS, months

Hazard ratio (95% CI)

71.9 69.8

0.95 (0.70–1.29)

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OS in the HRp population

16

Data cut-off date: 8 April 2024; median duration of follow-up: 6.2 years.

CI = confidence interval; HRp = homologous recombination proficient; OS = overall survival; yr = year. Monk BJ, et al. Ann Oncol 2024:S0923–7534(24)03762–1 (Supplementary information).

OS in HRp

Overall survival (%)

0

10

20

30

40

50

60

100

90

80

70

Niraparib

Placebo

0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88

Months since randomization

3-yr OS rate:

52% vs 42%

4-yr OS rate:

37% vs 33%

5-yr OS rate: 29% vs 27%

Results should be interpreted with caution because the study was not designed to evaluate treatment effect specifically in this subgroup (small sample sizes, impacts to stratification factors, and retrospective nature), and no formal testing was performed.

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Several factors impact clinical interpretation when evaluating PFS and OS outcomes

The following factors potentially confound interpretation of OS:

OS = overall survival; PARPi = poly(ADP-ribose) polymerase inhibitor; PFS = progression-free survival. Matulonis UA, et al. Cancer 2015;121:1737–46.

​

Extended post-progression survival

​

High rates of post-progression PARPi treatment

Higher risk patient population included in PRIMA

1

2

3

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In PRIMA the post-progression survival exceeded 32 months in the overall population

35

PPS was calculated as OS - PFS.

1L = first-line; CT = chemotherapy; HRd = homologous recombination deficient; HRp = homologous recombination proficient; ITT = intention-to-treat; OC = ovarian cancer; OS = overall survival; PARPi = poly(ADP-ribose) polymerase inhibitor; PFS = progression-free survival; PPS = post-progression survival

1. Monk BJ, et al. Ann Oncol 2024:S0923–7534(24)03762–1. 2. Broglio KR and Berry DA. J Natl Cancer Inst 2009;101:1642–9. 3. Matulonis UA, et al. Cancer 2015;121:1737–46.

71.9

69.8

13.8

46.6

8.2

48.8

0

10

20

30

60

70

80

PFS PFS

OS OS

PPS PPS

Placebo arm: PARPi arm:

40 50

Months

Niraparib

Placebo

OS

PFS/PPS OS PFS/PPS

Niraparib

Placebo

OS

Niraparib

Placebo

ITT

population¹

HRd population¹

HRp population¹

• With longer post-progression time, patient heterogeneity and post-progression treatment can dilute differences in OS between treatment arms. Post-progression survival ranged from approximately 3–4 years in the ITT and HRd populations of the PRIMA trial

1^st LINE

Several factors impact clinical interpretation when evaluating PFS and OS outcomes

36

The following factors potentially confound interpretation of OS:

OS = overall survival; PARPi = poly(ADP-ribose) polymerase inhibitor; PFS = progression-free survival. Matulonis UA, et al. Cancer 2015;121:1737–46.

₁ Extended post-progression survival

​

High rates of post-progression PARPi treatment

2

₃ Higher risk patient population included in PRIMA

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Subsequent PARPi use was high in the placebo arm (38%) and predominantly in the second-line treatment setting

21

Subsequent PARPi therapy^a

37.8

48.4

57.7

36.4

18.8

25

50

75

100

HRd

Overall

HRd/BRCAm

HRd/BRCAwt

HRp

Patients, %

57/487 93/246

^39/247 61/126

HRd (all)

29/152 41/71

10/94 20/55

10/169 15/80

0

n/N

11.7

15.8

19.1

10.6

5.9

Niraparib Placebo

Data cut-off date: 8 April 2024; median duration of follow-up: 6.2 years.

^aPercentages calculated out of the number of patients who received subsequent PARPi therapy.

2L = second-line; 3L = third-line; BRCA = breast cancer gene; BRCAm = BRCA mutant; BRCAwt = BRCA wild type; HRd = homologous recombination deficient; HRp = homologous recombination proficient; PARPi = poly(ADP-ribose) polymerase inhibitor.

González-Martín A, et al. presented at ESMO 2024 (abstract LBA29), 13–17 September, Barcelona, Spain.

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Several factors impact clinical interpretation when evaluating PFS and OS outcomes

46

OS = overall survival; PARPi = poly(ADP-ribose) polymerase inhibitor; PFS = progression-free survival. Matulonis UA, et al. Cancer 2015;121:1737–46.

₁ Extended post-progression survival

₂ High rates of post-progression PARPi treatment

Higher risk patient population included in PRIMA

3

1^st LINE

It is important to understand differences in patient populations among 1LM PARPi trials

*PRIMA did not include patients with stage III R0 after PCS

• Stage IV disease
• Visible residual disease or no surgery
• ICS/NACT or no surgery
• PR to chemotherapy
• BRCAwt, BRCAnd, or missing

High-risk factors:^a,1,2

CLINICAL RISK

1^st LINE

SOLO1 trial design

SOLO1 is a randomized, double-blind, placebo-controlled, Phase 3 trial of olaparib maintenance therapy in patients

with BRCAm advanced ovarian cancer following 1L platinum-based chemotherapy^1,2

n=391

​

Olaparib (tablets) 300 mg PO BID

n=260

n=131

Placebo BID

R

2:1

​

• Newly diagnosed, FIGO stage III-IV, high- grade serous or endometroid ovarian, primary peritoneal or fallopian tube cancer¹
• Only patients with documented germline

or somatic deleterious BRCA mutation¹

• In CR or PR at end of frontline

platinum-based chemotherapy including patients with no residual disease¹

• ECOG performance status 0–1
• Cytoreductive surgery^a
• In clinical complete^b or partial response after platinum-based chemotherapy¹

​

Up to 2 years^c or until progression

Radiologic scans ~12 weeks up to 3 years and every

~24 weeks thereafter until progression

Stratification factors:

• Outcome at 1L CT (CR or PR)

​

Up to 2 years^c or until progression

Primary endpoint:

PFS (investigator-assessed by modified RECIST v1.1)

Secondary endpoints:

• PFS by BICR
• PFS2
• OS
• RFS
• Best ORR

• HRQoL
• TFST
• TSST
• Safety and tolerability

5

1^st LINE

Primary endpoint: Investigator-assessed PFS^a showed a sustained benefit with olaparib vs placebo (5-year follow-up)

FOR REACTIVE USE ONLY

Patients free from disease progression and death (%)

No. at risk

(Number censored)

0

0

10

30

20

50

40

60

70

90

80

100

6

12

18

60

66

72

78

88%

74%

60%

52%

48%

51%

35%

27%

22%

21%

Median treatment duration (IQR):

Olaparib, 24.6 months (11.2–24.9)

Placebo, 13.9 months^c (8.0–24.8)

2-year treatment cap^b

Placebo

Olaparib

Median follow-up for PFS (IQR): Olaparib: 4.8 years (2.8–5.3)

Placebo: 5.0 years (2.6–5.3)

5-year DCO

24 30 36 42 48 54

Time since randomization (months)

DCO: 5 Mar 2020 (5 years after last patient randomized). ^aInvestigator-assessed by modified RECIST v1.1; ^b13 patients, all in the olaparib arm, continued study treatment past 2 years;

^cn=130 (safety analysis set). CI = confidence interval; DCO = data cut-off; IQR = interquartile range; mPFS = median progression-free survival; NR = not reached; PARPi = poly(ADP- ribose)polymerase inhibitor; PFS = progression-free survival; RECIST = Response Evaluation Criteria In Solid Tumors. 1. Banerjee S, et al. Lancet Oncol 2021;22:1034–46; 2. Banerjee S, et al. presented at ESMO 2020, 19–21 Sep (virtual).

14

1^st LINE

SOLO-1 OS data ^1,2

73.1%

63.4%

46.5%

67.0%

Olaparib

Placebo

46

FOR REACTIVE USE ONLY

CI = confidence interval; NR = not reached; OS = overall survival; PARP = poly(ADP-ribose)polymerase.

1. DiSilvestro P, et al. Presented at ESMO 2022, 9–13 Sep, Paris, France; 2. DiSilvestro P, et al. J Clin Oncol 2023;41:609–17.

0

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102

100

90

80

70

60

50

40

30

20

10

Overall survival (%)

44.3% of patients in the placebo group received subsequent PARP inhibitor therapy, compared with 14.6% of patients in the olaparib group

Data cut-off: 7 Mar 2022; ^aDescriptive OS analysis; P<0.0001 required to declare statistical significance as per the statistical analysis plan.

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The most frequent TEAEs in the olaparib arm were nausea, fatigue/asthenia,

vomiting and anemia^1,2a

50

77.7

64.2 3.8

25.8

23.1

37.7

30.0

20.4

15.4

0.8

24.6

10.0

0.8

1.5

8.5

2.3

3.8

1.5

1.5 10.0

41.5

14.6

19.2

19.2

Nausea Fatigue/asthenia^b

Vomiting Anemia^b Diarrhea Arthralgia Constipation Abdominal pain

Headache Neutropenia^b Dysgeusia Dizziness Decreased appetite

Cough

23.8

4.6 11.5

^40.0 0.4

40.0 21.9

34.6 3.1

28.8

27.7

23.1

21.5

0.8

20.4

^16.9 21.5

90 80 70 60 50 40 30 20 10 00 10 20 30 40 50 60 70

Patients with TEAEs (%)

Olaparib (N=260)

Placebo (N=130)

0.8

0.4

All Grades

Grade ≥3 All Grades Grade ≥3

1. DiSilvestro P, et al. Presented at ESMO 2022, 9–13 Sep, Paris, France; 2. DiSilvestro P, et al. J Clin Oncol 2023;41:609–17.

FOR REACTIVE USE ONLY

Data cut-off: 7 Mar 2022; ^aAll grades, frequency ≥20% in either treatment arm; ^bGrouped-term TEAEs. All-grade thrombocytopenia (grouped term) occurred in 11.2% of patients in the olaparib group and 3.8% of patients in the placebo group and Grade ≥3 thrombocytopenia (grouped term) occurred in 0.8% and 1.5%, respectively. TEAE = treatment-emergent adverse event.

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PAOLA-1: Trial design

53

​

​

Patients

• Newly diagnosed, FIGO stage III–IV high-grade serous or endometrioid ovarian, fallopian tube and/or primary peritoneal cancer^a

​

1L treatment

• Upfront or interval surgery
• Platinum-taxane based chemotherapy plus ≥2 cycles of bevacizumab^b,c

NED/CR/PR

2:1 randomization stratified by:

• Tumor BRCAm status
• 1L treatment outcome^e

≤9 weeks

Olaparib tablets 300 mg BID x 2 years

Placebo x 2 years

+ bevacizumab^d

+ bevacizumab^d

Primary endpoint

• Investigator-assessed

PFS (RECIST v1.1)

Secondary points included:

• PFS2
• OS
• TFST
• TSST

Maintenance therapy

FOR REACTIVE USE ONLY

González-Martín A, et al. Presented at ESMO Gyn 2023; 23–24 Feb, Barcelona, Spain.

Maintenance Olaparib plus bevacizumab in patients with newly diagnosed advanced ovarian cancer

1^st LINE

PFS olaparib + bevacizumab in the ITT population and in patients with tBRCAm tumors

Probability of PFS (%)

Patients at risk Olaparib + bev Placebo + bev

100

90

80

70

60

50

40

30

20

10

0

72

80

Placebo + bev

5-year PFS rate^a (95% CI) Olaparib + bev

29% (25–33)

16% (12–21)

0 12 24 36 48 60

​

Months since randomization

537 513 462 434 404 376 322 293 243 233 204 197 187 168 160 153 150 143 130 93 75 46 36 9 5 3 0

269 ^{253 227 205 172 151 120 96 76 69} 60 55 53 46 ^{45 44 40 38} 34 26 ²² 13 10 3 ⁰

Patients. at risk

Olaparib + bev Placebo + bev

Placebo + bev

ITT population 100 tBRCAm

90

80

70

60

50

40

30

20

10

0

0 12 24 36 48 60 72

Months since randomization

157 154 150 148 144 138 131 125 116 113 102 98 96 86 85 82 80 78 70 50 40 27 22 8 4 2 0

80 79 73 66 59 52 45 40 32 28 27 25 24 21 20 20 19 18 17 12 10 6 5 1 0

80

^aCalculated by KM estimates. Bev = bevacizumab; CI = confidence interval; ITT = intention to treat; KM = Kaplan–Meier; PFS = progression-free survival; tBRCAm = tumor breast cancer gene mutant.

56

González-Martín A, et al. Presented at ESMO Gyn 2023; 23–24 Feb, Barcelona, Spain.

FOR REACTIVE USE ONLY

Probability of PFS (%)

5-year PFS rate^a (95% CI) Olaparib + bev

50% (42–58)

25% (16–35)

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PFS olaparib + bevacizumab in patients with HRd tumors regardless of BRCAm status, but not in patients with HRp tumors

HRd

Probability of PFS (%)

HRd excluding tBRCAm

HRp

80

Patients at risk

100

90

80

70

60

50

40

30

20

10

0

0

12

24 36 48

Months since randomization

60

72

Placebo + bev

^{Olaparib + bev} 255252242236223214 194 183165162147143138 127123 119117112 103 79 63 40 31 8 5 3 0

^{Placebo + bev} 132129118103 91 79 62 52 41 37 34 30 29 25 24 24 21 20 19 15 13 8 6 2 0

100

90

80

70

60

50

40

30

20

10

0

0

12

24 36 48

Months since randomization

60

72

80

97 96 90 86 79 76 64 60 50 50 46 46 43 41 38 38 38 36 35 29 22 14 10 1 1 1 0

55 54 48 41 37 32 23 19 15 14 13 11 11 9 9 9 7 6 6 5 5 4 3 1 0

Placebo + bev

192175146129116103 78 65 39 34 26 24 20 15 15 13 12 11 11 7 7 3 2 0

85 79 68 63 52 47 36 23 16 16 12 11 11 9 9 9 8 8 7 5 4 2 2 1 0

100

90

80

70

60

50

40

30

20

10

0

0

12

24 36 48 60

Months since randomization

72

80

5-year PFS rate^a (95% CI) Olaparib + bev

46% (40–52)

tBRCAm = tumor breast cancer gene mutant.

González-Martín A, et al. Presented at ESMO Gyn 2023; 23–24 Feb, Barcelona, Spain.

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19% (13–27)

5-year PFS rate^a (95% CI) Olaparib + bev

41% (31–51)

15% (7–25)

5-year PFS rate^a (95% CI) Placebo + bev

12% (6–20)

Olaparib + bev 8% (5–13)

^aCalculated by Kaplan–Meier estimates. Bev = bevacizumab; CI = confidence interval; HRd = homologous recombination deficient; HRp = homologous recombination proficient; PFS = progression-free survival;

1^st LINE

OS in the ITT population

Patients receiving a PARP inhibitor during

any subsequent treatment Olaparib + bevacizumab: 19.6% (105/537) Placebo + bevacizumab: 45.7% (123/269)

Median time from first cycle of CT to randomization = 6 months

Patients at risk

Olaparib + bevacizumab 537 530 528 517 503 480 463 440 420 398 376 357 347 329 308 295 286 276 262 217 169 113 82 40 19 4 0

Placebo + bevacizumab 269 267 264 261 250 242 229 220 208 199 188 179 166 160 154 146 139 132 121 96 76 51 37 20 5 2 0

12

0

24 36 48

Time from randomization (months)

60

72 80

Patients who survived (%)

0

10

20

30

40

50

60

70

100

​

90

​

80

47.3%

CI = confidence interval; CT = chemotherapy; ITT = intention-to-treat; OS = overall survival; PARP = poly(ADP-ribose)polymerase. Ray-Coquard I, et al. Presented at ESMO 2022, 9–13 Sep, Paris, France.

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41.5%

5-year OS rate

Data cut-off: 22 Mar 2022.

Final overall survival results from the Phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced ovarian cancer

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OS in the HRd population

48.4%

5-year OS rate

65.5%

Data cut-off: 22 Mar 2022; ^aMedian unstable; <50% data maturity. HRd defined as a tBRCAm and/or genomic instability score of ≥42 on the Myriad myChoice HRD Plus assay. CI = confidence interval; HRD = homologous recombination deficiency; HRd = homologous recombination deficient; OS = overall survival; PARP = poly(ADP-ribose)polymerase;

12

0

tBRCAm = tumor breast cancer gene mutant.

Ray-Coquard I, et al. Presented at ESMO 2022, 9–13 Sep, Paris, France.

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24 36 48

Time from randomization (months)

60

72 80

Patients who survived (%)

0

10

20

30

40

60

​

50

70

80

100

​

90

Patients at risk

Olaparib + bevacizumab 255 253 253 252 252 244 238 231 225 215 205 200 195 189 183 176 174 170 164 142 116 83 62 32 17 4 0

Placebo + bevacizumab 132 130 129 128 126 121 117 114 109 105 100 96 91 89 86 82 79 77 70 59 44 29 21 9 2 1 0

Patients receiving a PARP inhibitor during

any subsequent treatment Olaparib + bevacizumab: 17.3% (44/255) Placebo + bevacizumab: 50.8% (67/132)

1^st LINE

OS in patients with HRd tumors regardless of BRCAm status & in patients with HRp tumors

BRCAm^a

HRd^c excluding BRCAm