A Phase III Study Comparing Single-Agent Olaparib or the Combination of Cediranib and Olaparib to Standard Platinum-Based Chemotherapy in Women With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Platinum sensitive high grade serous or endometrioid ovarian cancer or germline BRCA1/2-mutated ovarian cancer, no prior PARP inhibitor

565, median 1 prior therapy

Recurrence

Open-Label, Randomized

ORR, PFS, OS, evaluated per RECIST

Exploratory: BROCA-HR

Ola+Ced (n=189) vs Ola (n=189) vs Treatment of Physician's Choice (TPC) (CarboPt+Gem (27%)/PLD (48%)/Pac (25%), n=187):

ORR: 69.4 vs 52.4 vs 71.3%
PFS: 10.4 vs 8.2 vs 10.3 months, HR: 0.86 (0.66-1.11, p=0.077); HR: 1.20 (0.93-1.54)
OS: 33.5 vs 31.0 vs 32.7 months

Exploratory analysis, gBRCA status, HRR status, LOH status:
gBRCA MUT: ORR: 89 vs 90 vs 71%; PFS: 18.0 vs 12.7 vs 10.5 months, HR: 0.55 (0.32-0.94); HR: 0.63 (0.37-1.07)
gBRCA WT: ORR: 64 vs 40 vs 72%; PFS: 8.9 vs 6.6 vs 9.7 months, HR: 0.97 (0.73-1.30); HR: 1.41 (1.07-1.81)
HRR mut: PFS: 20.4 vs 13.1 vs 12.3 months, HR: 0.55 (0.32-0.95); HR: 0.78 (0.48-1.27)
HRR wt: PFS: 8.5 vs 6.4 vs 9 months, HR: 0.93 (0.68-1.27); HR: 1.56 (1.15-2.12) 
LOH high: PFS: 12.2 vs 8.5 vs 10.6 months
LOH low: PFS: 8.4 vs 6.3 vs 8.1 months

Ola+Ced vs Ola vs TPC:
Serious AE:
Grade 3-4 AE: neutropenia (3.8 vs 1.6 vs 31.8%), anemia (5.5 vs.15.0 vs 13.8%), thrombocytopenia (1.6 vs 1.0 vs 15.0%), leukopenia (1.1 vs 1.1 vs 14.4%), fatigue (17.5 vs 7.0 vs 1.8%), diarrhea (13.7 vs 1.0 vs 1.8%), hypertension (31.7 vs 5.3 vs 1.8%)

Cediranib+olaparib has similar activity to standard of care in relapsed platinum sensitive ovarian cancer but does not improve PFS or OS

Liu J et al. Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial. J Clin Oncol (2022) 40(19):2138-2147
https://pubmed.ncbi.nlm.nih.gov/35290101/

Liu JF et al. Overall survival (OS) outcomes from NRG-GY004, a phase III study comparing single-agent olaparib or combination cediranib and olaparib to platinum (Plat) based chemotherapy in recurrent plat sensitive ovarian cancer (OvCa). Ann Oncol (2023) 34(2) abstract LBA45
https://www.clearityfoundation.org/wp-content/uploads/2023/11/NRG-GY004-abstract-ESMO-2023.pdf