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.