overview of ongoing first- line trials in ovarian …...why is it so hard to show a survival benefit...
TRANSCRIPT
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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
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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
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Current Front-Line Trials in Ovarian Cancer
Naumann RW, Gynecol Oncol. 153(2):436-444, 2019
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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
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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
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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
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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?
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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%
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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.
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Rationale for PARPi use in primary therapy Effect after platinum sensitive relapse
ARIEL NOVA
HR 0.36 HR 0.45
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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
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Upcoming Positive Trials During Chemo Maintenance
Naumann RW, Gynecol Oncol. 153(2):436-444, 2019
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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?
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Upcoming Positive Trials
Different Randomization times! Different comparators!
Different durations !
Naumann RW, Gynecol Oncol. 153(2):436-444, 2019
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Rationale for other combinations
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PARPi Maintenance
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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
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AVANOVA
Mirza MR, J Clin Oncol 37, 2019 (suppl; abstr 5505) NCT02354131
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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
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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
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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.
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ARIEL3: Investigator-Assessed PFS
Coleman RL, et al. Lancet. 2017;390:1949-1961.
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Coleman RL, et al. Lancet. 2017;390:1949-1961.
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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
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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)
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Mirza MR, et al. N Engl J Med. 2016;375:2154-2164.
NOVA: PFS gBRCAmut Non-gBRCAmut Non-gBRCAmut HRD+
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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%
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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
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Niraparib + PD-1 Inhibitor Treatment Resulted in Clinical Activity Across a Broad Study
Population
37 Panagiotis Konstantinopoulos ASCO 2018
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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
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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
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Combination Trials
APR, 2020
DEC, 2024
During Chemo Maintenance
Naumann RW, Gynecol Oncol. 153(2):436-444, 2019
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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
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Everything Trials During Chemo Maintenance
NOV, 2021
MAY, 2022
AUG, 2025
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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.