A Phase 2, Open-Label Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)

Trial ID # NCT01891344; ARIEL2
Phase II
Drug Class DNA Damage Repair Pathway Inhibitors: PARP
Drug Name Rucaparib
Alternate Drug Names Rubraca, CO-338, PF 01367338, AG-014699
Drugs in Trial Rucaparib
Eligible Participant

Recurrent high grade ovarian cancer

Patients Enrolled

491

Therapy Setting

Recurrence

Study Design

Open-Label, Non-randomized

Endpoints

ORR, PFS, evaluated per RECIST

Biomarkers

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

Efficacy

BRCA MUT (n=138) vs BRCA WT LOH high (n=156) vs BRCA WT LOH low (n=168):
ORR: 45.7 vs 16.7 vs 7.7%
PFS: 7.8 vs 4.3 vs 4.0 months, HR: 0.47 (0.37-0.60, p<0.0001); HR: 0.78 (0.62-0.98, p=0.037)

Pt-S vs Pt-R/Pt-Rf:
PFS: 9.4 vs 7.2 months, HR: 0.44 (0.30-0.63, p<0.001)

1-2 prior therapies, BRCA MUT (n=31) vs BRCA WT LOH high (n=57) vs BRCA WT LOH low (n=74):
ORR: 87.1 vs 35.1 vs 9.5%

≥3 prior therapies, BRCA MUT (n=107) vs BRCA WT LOH high (n=99) vs BRCA WT LOH low (n=94):
ORR: 33.6 vs 6.1 vs 6.4%

Pt-SBRCA MUT (n=74) vs BRCA WT LOH high (n=83) vs BRCA WT LOH low (n=112):
ORR: 64.9 vs 27.7 vs 8.9%
PFS: 9.4 vs 7.2 vs 5.3 months

Pt-R/Pt-RfBRCA MUT (n=64) vs BRCA WT LOH high (n=73) vs BRCA WT LOH low (n=56):
ORR: 23.4 vs 4.1 vs 5.4%
PFS: 7.2 vs 1.9 vs 1.8 months

Clinically Significant Adverse Events

Serious AE: none
Grade 3-4 AE: anemia or decreased hemoglobin (22%), elevated liver enzymes (13%)

Conclusion

Administration of rucaparib as active treatment should be considered in earlier lines of therapy before the emergence of platinum resistance. RAD51C/D mutation and high-level BRCA1 promotor methylation predict response to rucaparib, similar to BRCA1/2 mutations, but LOH high is only predictive of response in platinum-sensitive patients

Reference

Swisher EM et al. Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2). Nat Commun (2021) 12(1):2487
https://pubmed.ncbi.nlm.nih.gov/33941784/

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