Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous and Endometrioid Ovarian Cancer (ARIEL3)

Trial ID # NCT01968213; ARIEL3
Phase III
Drug Class DNA Damage Repair Pathway Inhibitors:PARP
Drug Name Rucaparib
Alternate Drug Names AG-014699, PF 01367338, CO-338, Rubraca
Drugs in Trial Rucaparib
Eligible Participant

Platinum-sensitive recurrence and CR or PR in most recent Pt-based therapy, ≥ 2 Pt-based regimens

Patients Enrolled

564

Therapy Setting

Maintenance

Study Design

Double Blind, Randomized

Endpoints

PFS, evaluated per RECIST

Biomarkers

Exploratory: BRCA1/2; LOH (by FoundationFocus CDx BRCA LOH)

Efficacy

Ruc maint vs Placebo (BICR):

All (n=564):
PFS: 13.7 vs 5.4 months, HR: 0.35 (0.28-0.45, p<0.0001)
BRCA MUT (n=196):
PFS: 26.8 vs 5.4 months, HR: 0.20 (0.13-0.32, p<0.0001)
BRCA MUT/BRCA WT LOH high (n=354):
PFS: 22.9 vs 5.5 months, HR: 0.34 (0.24-0.47, p<0.0001)

Exploratory analysis BRCA WT patients:
BRCA WT/LOH low (n=161): PFS: 8.2 vs 5.3 months, HR: 0.47 (0.31-0.71, p=0.0002)
BRCA WT/LOH high (n=158): PFS: 11.1 vs 5.6 months, HR: 0.55 (0.35-0.89, p=0.0135)

Ruc maint vs Placebo (investigator review):

All (n=564):
PFS: 10.8 vs 5.4 months, HR: 0.36 (0.30-0.45, p<0.0001)
BRCA MUT (n=196):
PFS: 16.6 vs 5.4 months, HR: 0.23 (0.16-0.34, p<0.0001)
BRCA MUT/BRCA WT LOH high (n=354):
PFS: 13.6 vs 5.4 months, HR: 0.32 (0.24-0.42, p<0.0001)

Exploratory analysis BRCA WT patients:
BRCA WT/LOH low (n=161): PFS: 6.7 vs 5.4 months, HR: 0.58 (0.40-0.85, p=0.0049)
BRCA WT/LOH high (n=158): PFS: 9.7 vs 5.4 months, HR: 0.44 (0.29-0.66, p<0.001)

Clinically Significant Adverse Events

Ruc vs Placebo:
Serious AE: any (21 vs 11%), two treatment related deaths in Ruc arm (1 AML, 1 MDS)
Grade 3-4 AE: any (54 vs 14%), anemia (19 vs 1% ), elevated liver enzymes (11 vs 0%)

Conclusion

Improved PFS for all patients with rucaparib maintenance treatment

Reference

Coleman RL et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet (2017) 390(10106): 1949-1961)
https://www.ncbi.nlm.nih.gov/pubmed/28916367