overview of ongoing first- line trials in ovarian …...why is it so hard to show a survival benefit...

the break.

Overview of Ongoing First-Line Trials in Ovarian Cancer

R. Wendel Naumann, MD, FCOG, FACSProfessor, Dept of Ob/Gyn

Levine Cancer Institute, Atrium Health Charlotte, NC USA

Disclosure Astra Zeneca - consulting

BioSutro - consulting/research Bristol-Myers-Squib - consulting/research

Clovis - consulting Genentech - consulting/speaking

Janssen - consulting Merck (Endocyte) - consulting/research

Novocure - consulting OncoMed - consulting/research

Tesaro - consulting Eisai - consulting

Current Front-Line Trials in Ovarian Cancer

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

Trial

Current Front-Line Trials in Ovarian Cance r

Size Anti-angiogenic PARPi I/O

BOOST 800 Bevacizumab

SOLO-1 451 (2:1) Olaparib

VELIA/GOG 3005 1140 (1:1:1) Velaparib

PRIMA/ENGO ov26 620 (2:1) Niraparib

PAOLA/E ov25 806 (2:1) Bevacizumab Olaparib

JAVELIN 100 998 Avelumab

IMaGYN050/ E ov39/ G3015 1300 Bevacizumab Avelumab

ATHENA/ E ov45/G3020 1012 (1:1:4:4) Rucaparib Nivolumab

JAVELIN 100 PARP 720 Bevacizumab Talzaoparib Avelumab

FIRST/E ov44 960 (1:1:2) ± Bevacizumab Nirparib Dostarlimab

DUO-O/E ov46 1056 Bevacizumab Olarib Durvalumab

E ov43/MK7339 1086 ± Bevacizumab Olaparib Pembrolizumab

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

Current Front-Line Trials in Ovarian Cancer

Trial Size Anti-angiogenic

PARPi I/O

BOOST 800 Bevacizumab

SOLO-1 451 (2:1) Olaparib

Velia/GOG 3005 1140 (1:1:1) Velaparib

PRIMA/ENGO ov26 620 (2:1) Niraparib

PAOLA/E ov25 806 (2:1) Bevacizumab Olaparib

JAVELIN 100 998 Avelumab

IMaGYN050/ E ov39/ G3015 1300 Bevacizumab Avelumab

ATHENA/ E ov45/G3020 1012 (1:1:4:4) Rucaparib Nivolumab

JAVELIN 100 PARP 720 Bevacizumab Talzaoparib Avelumab

FIRST/E ov44 960 (1:1:2) ± Bevacizumab Niraparib Dostarlimab

DUO-O/E ov46 1056 Bevacizumab Olaparib Durvalumab

E ov43/MK7339 1086 ± Bevacizumab Olaparib Pembrolizumab

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

Current Front-Line Trials in Ovarian Cancer

Trial

Size Anti-angiogenic

PARPi I/O Completion

BOOST 800 Bevacizumab Unknown (est 11/18)

SOLO-1 451 Olaparib HR - 0.30 -> Reported 11/18

Velia/GOG 3005 1140 Velaparib Positive -> ? ESMO 2019

PRIMA/ENGO ov26 620 Niraparib Positive -> ? ESMO 2019

PAOLA/E ov25 806 Bevacizumab Olaparib Positive -> ? ESMO 2019

JAVELIN 100 998 Avelumab Closed for Futility 1/19

IMaGYN050/ E ov39/ G3015

1300 Bevacizumab Avelumab Completed Enrollment

ATHENA/ E ov45/G3020

1012 Rucaparib Nivolumab Enrolling (5/18)

JAVELIN 100 PARP 720 Bevacizumab Talzaoparib Avelumab Discontinued 4/19

FIRST/E ov44 960 ± Bevacizumab Nirparib Dostarlimab Enrolling (10/18)

DUO-O/E ov46 1056 Bevacizumab Olarib Durvalumab Enrolling (12/18)

E ov43/MK7339 1086 ± Bevacizumab Olaparib Pembrolizumab Enrolling (12/18)

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

What is it going to take to move the bar?

Hazard Ratio

0.72 0.60 0.30 0.50

+4 mo +7 mo +10 mo +24 mo

18 mo +6 mo +10 mo +16 mo +42 mo

Median PFS

10 mo

Toxicity? Cost?

Are we curing patients?

Platinum Sensitive Ovarian Cancer Maintenance Therapy Options

Recurrent Ovarian Cancer> 6 monthsfromcompletion ofchemotherapy

CHOICE

Chemotherapy + Bevacizumab-> Bevacizumab

Chemotherapy

Respond->PARPi

Progression->

Chemo

RR ~20% greater!PFS HR 0.48-0.60!

HR - 0.2-0.5!

Not included in Response HR!

Observation50%

56%

44%

Why is it so hard to show a Survival Benefit in Ovarian Cancer with these trials?

- Assume clinical trial of 280 pt- 80% to detect a HR of 0.66

- The agent used has no effect on time to Survival Post Progression (SPP)

PFS +3 month

How does the length of post-progression survival influence the ability of the trial to show an OS difference?

Broglio KR, JNCI 101(23):1642, 2009

Trial

Current Front-Line Trials in Ovarian Cance r

Size Anti-angiogenic PARPi I/O

BOOST 800 Bevacizumab

SOLO-1 451 (2:1) Olaparib

VELIA/GOG 3005 1140 (1:1:1) Velaparib

PRIMA/ENGO ov26 620 (2:1) Niraparib

JAVELIN 100 998 Avelumab

PAOLA/E ov25 806 (2:1) Bevacizumab Olaparib

IMaGYN050/ E ov39/ G3015 1300 Bevacizumab Avelumab

ATHENA/ E ov45/G3020 1012 (1:1:4:4) Rucaparib Nivolumab

JAVELIN 100 PARP 720 Bevacizumab Talzaoparib Avelumab

FIRST/E ov44 960 (1:1:2) ± Bevacizumab Nirparib Dostarlimab

DUO-O/E ov46 1056 Bevacizumab Olarib Durvalumab

E ov43/MK7339 1086 ± Bevacizumab Olaparib Pembrolizumab

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

Current Front-Line Trials in Ovarian Cancer

Trial Size Anti-angiogenic

PARPi I/O

BOOST 800 Bevacizumab

SOLO-1 451 (2:1) Olaparib

Velia/GOG 3005 1140 (1:1:1) Velaparib

PRIMA/ENGO ov26 620 (2:1) Niraparib

PAOLA/E ov25 806 (2:1) Bevacizumab Olaparib

JAVELIN 100 998 Avelumab

IMaGYN050/ E ov39/ G3015 1300 Bevacizumab Avelumab

ATHENA/ E ov45/G3020 1012 (1:1:4:4) Rucaparib Nivolumab

JAVELIN 100 PARP 720 Bevacizumab Talzaoparib Avelumab

FIRST/E ov44 960 (1:1:2) ± Bevacizumab Niraparib Dostarlimab

DUO-O/E ov46 1056 Bevacizumab Olaparib Durvalumab

E ov43/MK7339 1086 ± Bevacizumab Olaparib Pembrolizumab

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

Burger RA, J Clin Oncol 2010;28(18S): Abstr LBA1

Previouslyuntreatedepithelialovarian,primaryperitoneal,orfallopiantube

cancer

• StageIIIop>mal(macroscopic)

• StageIIIsubop>mal• StageIV

RANDOMIZE

Bevacizumab 15 mg/kg d1

Control arm:Carbopla>nAUC6d1

Paclitaxel175mg/m2d1Placebo d1

Q 21 days x 6 courses

n = 1873Placebo

x 16 cyclesExperimental arm:Carbopla>nAUC6IVd1

Paclitaxel 175 mg/m2 IV d 1Bevacizumab 15 mg/kg d1

Experimental arm: Carboplatin AUC 6 IV d 1

Paclitaxel 175 mg/m2 IV d 1

MaintenanceB

evacizumab

x 16 cycles

Stra%fica%onvariables:

• GOGperformancestatus

• Stage/debulkingstatus

GOG 218 Study Scheme Bevacizumab during Treatment and as Maintenance

GOG 218 Does this move the bar and rationale for the BOOST trial Bevacizumab during Treatment and as Maintenance

Arm I CP + PLA →

PLA (n=625)

Arm IICP + BEV → PLA

(n=625)

Arm IIICP + BEV → BEV

(n=623)

Patients with event, n (%) 375(60) 405(67) 363(71)

Median PFS, months 10.4 11.5 13.9

HR (stratified)�(95% CI)

0.864(0.759–0.996)

0.726 (0.627–0.840)

One-sided log-rank p-value 0.0218* <0.0001aMedianfollow-up:17.4months

Burger RA, J Clin Oncol 2010;28(18S): Abstr LBA1

Bevacizumab

Benefit lost after stopping

Current Front-Line Trials in Ovarian Cancer

Trial

Size Anti-angiogenic PARPi I/O

BOOST 800 Bevacizumab

SOLO-1 451 (2:1) Olaparib

VELIA/GOG 3005 1140 (1:1:1) Velaparib

PRIMA/ENGO ov26 620 (2:1) Niraparib

JAVELIN 100 998 Avelumab

PAOLA/E ov25 806 (2:1) Bevacizumab Olaparib

IMaGYN050/ E ov39/ G3015 1300 Bevacizumab Avelumab

ATHENA/ E ov45/G3020 1012 (1:1:4:4) Rucaparib Nivolumab

JAVELIN 100 PARP 720 Bevacizumab Talzaoparib Avelumab

FIRST/E ov44 960 (1:1:2) ± Bevacizumab Nirparib Dostarlimab

DUO-O/E ov46 1056 Bevacizumab Olarib Durvalumab

E ov43/MK7339 1086 ± Bevacizumab Olaparib Pembrolizuma

b Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

Current Front-Line Trials in Ovarian Cancer

Trial Size Anti-angiogenic

PARPi I/O

BOOST 800 Bevacizumab

SOLO-1 451 (2:1) Olaparib

Velia/GOG 3005 1140 (1:1:1) Velaparib

PRIMA/ENGO ov26 620 (2:1) Niraparib

PAOLA/E ov25 806 (2:1) Bevacizumab Olaparib

JAVELIN 100 998 Avelumab

IMaGYN050/ E ov39/ G3015 1300 Bevacizumab Avelumab

ATHENA/ E ov45/G3020 1012 (1:1:4:4) Rucaparib Nivolumab

JAVELIN 100 PARP 720 Bevacizumab Talzaoparib Avelumab

FIRST/E ov44 960 (1:1:2) ± Bevacizumab Niraparib Dostarlimab

DUO-O/E ov46 1056 Bevacizumab Olaparib Durvalumab

E ov43/MK7339 1086 ± Bevacizumab Olaparib Pembrolizumab

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

Moore K, et al. N. Engl J Med 2018;379:2495-2505.

First-Line Maintenance: SOLO-1 Trial

• Newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III/IV, high-grade serous or endometroid ovarian, primary peritoneal,or fallopian tube cancer

• Germline or somatic BRCAm• Eastern Cooperative

Oncology Group performance status(ECOG PS) 0-1

• Cytoreductive surgery• In clinical CR or PR after

platinum-based chemotherapy

Olaparib 300 mg bd

(N=260)

2:1 randomization Stratified by response

to platinum-based chemotherapy

Placebo (N=131)

Primary Endpoint

Secondary Endpoints

• Investigator-assessed PFS(modified RECIST 1.1)

• PFS using blinded independentcentral review (BICR)

• PFS after next line of treatment(PFS2)

• OS• Time from randomization to first

subsequent therapy or death(TFST)

• Time from randomization tosecond subsequent therapy ordeath (TSST)

• Health-related quality of life(HRQoL) (Function Assessment of Cancer Therapy-O vary trial outcome index [FACT-O TOI] score

Two years’ treatment if no evidence of disease

• Study treatment continued until disease progression

• Patients with no evidence of disease at 2 years stopped treatment

• Patients with PR at 2 years could continue treatment

Study Design

Moore K, et al. N Engl J Med. 2018;379:2495-2505.

SOLO-1: PFS Olaparib

(N=260)

Placebo (N=131)

Events (%) [50.6% maturity]

102 (39.2) 96 (73.3)

Median PFS, mo NR 13.8

HR 0.30

95% CI 0.23, 0.41; P<0.0001

SOLO-1: Reflections Olaparib (N=260)

Placebo (N=131)

Events (%) [50.6% maturity]

102 (39.2) 96 (73.3)

Median PFS, mo NR 13.8

HR 0.30

95% CI 0.23, 0.41; P<0.0001

Same HR as SOLO-2

PFS only 13.8 mo

18% of patients had PR to 1st line chemo!

Benefit continues!

Olaparib 300 mg bid

Curve flattens!

Moore K, et al. N Engl J Med. 2018;379:2495-2505.

Rationale for PARPi use in primary therapy Effect after platinum sensitive relapse

ARIEL NOVA

HR 0.36 HR 0.45

Current Front-Line Trials in Ovarian Cancer

Trial Size Anti-angiogenic

PARPi I/O

BOOST 800 Bevacizumab

SOLO-1 451 (2:1) Olaparib

Velia/GOG 3005 1140 (1:1:1) Velaparib

PRIMA/ENGO ov26 620 (2:1) Niraparib

PAOLA/E ov25 806 (2:1) Bevacizumab Olaparib

JAVELIN 100 998 Avelumab

IMaGYN050/ E ov39/ G3015 1300 Bevacizumab Avelumab

ATHENA/ E ov45/G3020 1012 (1:1:4:4) Rucaparib Nivolumab

JAVELIN 100 PARP 720 Bevacizumab Talzaoparib Avelumab

FIRST/E ov44 960 (1:1:2) ± Bevacizumab Niraparib Dostarlimab

DUO-O/E ov46 1056 Bevacizumab Olaparib Durvalumab

E ov43/MK7339 1086 ± Bevacizumab Olaparib Pembrolizumab

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

Upcoming Positive Trials During Chemo Maintenance

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

What is it going to take to move the bar?

Hazard Ratio

0.72 0.60 0.30 0.50

+4 mo +7 mo +10 mo +24 mo

18 mo +6 mo +10 mo +16 mo +42 mo

Median PFS10 mo

Toxicity? Cost?

Are we curing patients?

Upcoming Positive Trials

Different Randomization times! Different comparators!

Different durations !

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

Rationale for other combinations

PARPi Maintenance

Combination of niraparib and bevacizumab versus niraparib alone as treatment of recurrent platinum-sensitive ovarian cancer: A randomized controlled chemotherapy-free study—NSGO-AVANOVA2/ENGOT-OV24 randomized, open-label, phase 2 study, women with measurable/evaluable, high-grade serous or endometrioid PSROC were randomized to niraparib 300mg once daily or the combination of niraparib 300mg once daily and BEV 15mg/kg IV every 3 weeks until disease progression (1:1 randomization)

Mirza MR, J Clin Oncol 37, 2019 (suppl; abstr 5505) NCT02 354131

Recurrent EOC High grade EOC>6 mo from PltNo limit on

chemoPrior Bev

allowed

R A N D O M I Z E

PFS

n= 97!

n= 48!

n= 49! Secondary Endpoints!PFS!

Safety!

Stratification!-6 to 12 mo vs > 12 mo PFI!-HRD status!

1:1

Niraparib 300 mg q d

Niraparib 300 mg q dBevacizumab 15 mg/Kg IV q 3 wk 11.9 mo

5.5 mo

HR = 0.35; (95% CI 0.21 to 0.57); P<0.001

AVANOVA

Mirza MR, J Clin Oncol 37, 2019 (suppl; abstr 5505) NCT02354131

TOPACIO Is a Phase 1/2 Study in Patients with PROC

TOPACIO Ovarian Cancer Patient Eligibility

• Response lasting ≥6 months to first-lineplatinum

• Considered platinum-resistant byinvestigator assessment

• Patients with platinum-sensitivedisease who were not eligible forfurther platinum (platinum ineligible)were allowed

• Secondary platinum-refractory diseaseallowed

• ≤5 prior lines of treatment

Determination of RP2D

Phas

e 1

Panagiotis Konstantinopoulos ASCO 2018

Phas

e 2 RP2D

Niraparib 200 mg + Pembrolizumab 200 mg

Endpoint Assessment

Primary Endpoint ORR by RECIST 1.1

Dose 1 Niraparib 200 mg +

Pembrolizumab 200 mg

Dose 2 Niraparib 300 mg +

Pembrolizumab 200 mg

PROC, platinum-resistant/refractory ovarian cancerORR, objective response rate RP2D, recommended phase 2 dose

Study Purpose: Evaluate the hypothesis that a PARPi combined with an anti-PD-1 will yield more robust efficacy than historical comparison to either drug alone in difficult-to-treat patient populations

Response All (%)

tBRCAmut (%)

HRDpos* (%)

tBRCAwt (%)

HRDneg (%)

ORR 11/47 (23%) 2/8 (25%) 4/16 (25%) 9/37 (24%) 7/26 (27%)

DCR 30/47 (64%) 5/8 (63%) 11/16 (69%) 24/37 (65%) 15/26 (58%)

*HRDpos includes BRCA mutation or HRD score ≥42 per Myriad assay.Patients with inconclusive biomarker results were not included in the biomarker subpopulations.Responses include confirmed and unconfirmed responses.

Clinical Activity Is Observed Across Biomarker Populations in Patients with Platinum-Resistant/Refractory Disease

• The addition of pembrolizumab to niraparib in tBRCAwt andHRDneg led to ORR similar to PARPi efficacy in the tBRCAmutpopulation

• HRD status does not correlate with response to thiscombination in platinum-resistant/-refractory disease Panagiotis Konstantinopoulos

ASCO 2018

ARIEL3: Study Design

Primary endpoint: Investigator-assessed PFS (per RECIST)Key secondary endpoints:

• BICR-assessed PFS• PFS by LOH status in patients with BRCA wt ovarian cancer• Overall response rate (ORR) in patients with measurable

disease at baseline

• High-grade serous or endometrial epithelialovarian cancer, primary peritoneal, orfallopian tube cancers

• Sensitive to penultimate platinum• Responding to most recent platinum (CR or

PR)• No prior PARPi

Rucaparib 600 mg bid

(n=375)

Placebo bid

(n=189)

R 2:1

Coleman RL, et al. Lancet. 2017;390:1949-1961.

30

ARIEL3: Investigator-Assessed PFS

Coleman RL, et al. Lancet. 2017;390:1949-1961.

31

Coleman RL, et al. Lancet. 2017;390:1949-1961.

32

ARIEL3: Investigator-Assessed ORR for Patients With Measurable Disease

BRCA Mutant Recombination Homologous

Deficiency (HRD) ITT

Response, % Rucaparib (n=40)

Placebo (n=23)

Rucaparib (n=40)

Placebo (n=23)

Rucaparib

(n=40)

Placebo (n=23)

RECIST ORR 37.5* 8.7 27.1* 7.3 18.4* 7.6

CR 17.5 0 11.8 0 7.1 1.5

PR 20.0 8.7 15.3 7.3 11.3 6.1

SD 47.5 34.8 50.6 41.5 50.4 43.9

PD 12.5 56.5 21.2 51.2 27.0 48.5

Not Evaluable 2.5 0 1.2 0 4.3 0 *Cochran-Mantel-Haenszel P<0.05 vs placebo.SD=stable diseasePD=progressive disease

Mirza MR, et al. N Engl J Med. 2016;375:2154-2164. ClinicalTrials.gov. NCT01847274. https://clinicaltrials.gov/ct2/show/NCT01847274. Accessed May 2, 2019.

Niraparib: NOVA Phase 3 Maintenance Study in Platinum-Sensitive Ovarian Cancer

33

• Platinum-sensitive ovarian, primaryperitoneal,or fallopian tube cancer

• Serous high-grade histology or known tohave gBRCAmut

• ≥2 prior platinum regimens• In CR or PR and enrolled within 8 weeks of

completion of last platinum regimen • No prior PARPi• Planned N=490

Niraparib 300 mg PO qd to progression

Placebo qd to progression

R 2:1

N=490Primary endpoint: PFSSecondary endpoints: OS, PFS2, chemotherapy-free interval, HRQoL, and safety and tolerabilityAnalysis to include all patients, gBRCAmut patients, and the non-gBRCAmut cohort (first as HRD+ patients and then all non-gBRCAmut patients)

Mirza MR, et al. N Engl J Med. 2016;375:2154-2164.

NOVA: PFS gBRCAmut Non-gBRCAmut Non-gBRCAmut HRD+

34

Platinum Sensitive Ovarian Cancer Maintenance Therapy Options

35

Recurrent Ovarian Cancer> 6 months

fromcompletion of chemotherapy

CHOICE

Chemotherapy + Bevacizumab-> Bevacizumab

Chemotherapy

Respond->PARPi

Progression->

Chemo

RR ~20% greater!PFS HR 0.48-0.60!

HR - 0.2-0.5!

Not included in Response HR!44%

56%

Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase III SOLO3 trial.

36 Penson RT, J Clin Oncol 37, 2019 (suppl; abstr 5506)

Recurrent EOCGermline BRCA≤ 2 prior Chemo>6 mo from Plt

R A N D O M I Z E

BICR

ORR

n= 266!

n= 178!

n= 54!

Secondary Endpoints!PFS!

Safety!

Stratification!-Prior lines of chemo (2-3 vs ≤ 4)!-advanced vs recurrent!

2:1

NCT02282020

Olaparib 300 mg bid

Physician Choice-Paclitaxel 80 mg/m2 D1,8,15, 22 q 28-Topotecan 4 mg/m2 D1,8,15 q 28d-Gemcitabine 1,000 mg D1, 8, 15 q 28 d-PLD 50 mg/m2 D1 q 28

Niraparib + PD-1 Inhibitor Treatment Resulted in Clinical Activity Across a Broad Study

Population

37 Panagiotis Konstantinopoulos ASCO 2018

Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase III SOLO3 trial.

• 266 gBRCAm PSR OC pts were randomized

- (olaparib, n=178; TPC, n=88 [PLD, n=47; P, n=20; G, n=13; T, n=8]

• ORR was 72% with olaparib vs 51% with chemo (OR 2.53, 95% CI 1.40–4.58; P=0.002)

• PFS by investigator assessment was 0.49 (95% CI 0.35–0.70; P<0.001;median 13.2 vs 8.5 months

• gBRCAm PSR OC receiving olaparib monotherapy had a significant,clinically relevant improvement in ORR and PFS vs Chemo

38 Penson RT, J Clin Oncol 37, 2019 (suppl; abstr 5506) NCT02282020

Current Front-Line Trials in Ovarian Cancer

Trial Size Anti-angiogenic

PARPi I/O

BOOST 800 Bevacizumab

SOLO-1 451 (2:1) Olaparib

Velia/GOG 3005 1140 (1:1:1) Velaparib

PRIMA/ENGO ov26 620 (2:1) Niraparib

PAOLA/E ov25 806 (2:1) Bevacizumab Olaparib

JAVELIN 100 998 Avelumab

IMaGYN050/ E ov39/ G3015 1300 Bevacizumab Avelumab

ATHENA/ E ov45/G3020 1012 (1:1:4:4) Rucaparib Nivolumab

JAVELIN 100 PARP 720 Bevacizumab Talzaoparib Avelumab

FIRST/E ov44 960 (1:1:2) ± Bevacizumab Niraparib Dostarlimab

DUO-O/E ov46 1056 Bevacizumab Olaparib Durvalumab

E ov43/MK7339 1086 ± Bevacizumab Olaparib Pembrolizumab

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

Combination Trials

APR, 2020

DEC, 2024

During Chemo Maintenance

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

Current Front-Line Trials in Ovarian Cancer

Naumann RW, Gynecol Oncol. 153(2):436-444, 2019

Trial Size Anti-angiogenic

PARPi I/O

BOOST 800 Bevacizumab

SOLO-1 451 (2:1) Olaparib

Velia/GOG 3005 1140 (1:1:1) Velaparib

PRIMA/ENGO ov26 620 (2:1) Niraparib

PAOLA/E ov25 806 (2:1) Bevacizumab Olaparib

JAVELIN 100 998 Avelumab

IMaGYN050/ E ov39/ G3015 1300 Bevacizumab Avelumab

ATHENA/ E ov45/G3020 1012 (1:1:4:4) Rucaparib Nivolumab

JAVELIN 100 PARP 720 Bevacizumab Talzaoparib Avelumab

FIRST/E ov44 960 (1:1:2) ± Bevacizumab Niraparib Dostarlimab

DUO-O/E ov46 1056 Bevacizumab Olaparib Durvalumab

E ov43/MK7339 1086 ± Bevacizumab Olaparib Pembrolizumab

Everything Trials During Chemo Maintenance

NOV, 2021

MAY, 2022

AUG, 2025

Future Challenges • Multiple positive trials

• What benefit at what cost?• How do we pick the winning strategy?

• What is the optimal therapy at recurrence• Does PARPi maintenance induce platinum

resistance• If previously treated with a PARPi is there an interval

of non-treatment where it makes sense to re-treatwith the same or similar agent.