ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): A Phase 3 Multicenter, Randomized Study of Rucaparib Versus Chemotherapy in Patients With Relapsed, BRCA Mutant, High Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Trial ID # NCT02855944; ARIEL4
Phase III
Drug Class DNA Damage Repair Pathway Inhibitors: PARP
Drug Name Rucaparib
Alternate Drug Names Rubraca, CO-338, PF 01367338, AG-014699
Drugs in Trial Carboplatin, Cisplatin, Gemcitabine, Paclitaxel, Rucaparib
Eligible Participant

Recurrent BRCA MUT ovarian cancer

Patients Enrolled

349; median 2 prior therapies; 21% Pt-S. 28% Part-Pt-S, 51% Pt-R; 6.6% w/ BRCA reversion mutation

Therapy Setting

Recurrence

Study Design

Open-Label, Randomized

Endpoints

ORR, DoR, PFS, evaluated per RECIST

Biomarkers

BRCA status

Efficacy

Ruc (n=205) vs Treatment of Physician's Choice (TPC) (n=105) (Monotherapy platinum (cisplatin or carboplatin) or platinum-based doublet chemotherapy (carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine or single agent paclitaxel):

ORR: 40.3 vs 32.3%, p=0.13
PFS: 7.4 vs 5.7 months, HR: 0.64 (0.49-0.84, p=0.001)
DoR: 9.4 vs 7.2 months, HR: 0.59 (0.36-0.98)

Exploratory analysis: w/ BRCA reversion mutation, Pt-status
w/ BRCA rev mut: Ruc (n=13) vs TPC (n=10): PFS2.9 vs 5.5 months
Pt-SRuc (n=48) vs TPC (n=26): ORR: 64 vs 57%; PFS: 12.9 vs 9.6 months
Part-Pt-SRuc (n=62) vs TPC (n=28): ORR: 53 vs 20%; PFS: 8.0 vs 5.5 months
Pt-RRuc (n=110) vs TPC (n=51): ORR: 23 vs 27%; PFS: 6.4 vs 5.7 months

Clinically Significant Adverse Events

Ruc vs TPC:
Serious AE: MDS/AML: 4 patients in Ruc arm (1 during treatment, 3 during long-term follow-up)
Grade 3-4 AE: anemia (22.4 vs 5.3%), neutropenia (10.3 vs 15.0%)

Conclusion

Recurrent BRCA MUT patients, including those who are platinum sensitive or platinum resistant, receive benefit with rucaparib treatment when compared to chemotherapy; the presence of a BRCA reversion mutation predicts for primary resistance to rucaparib

Reference

Kristeleit R et al. Rucaparib versus chemotherapy in patients with advanced, relapsed ovarian cancer and a deleterious BRCA mutation: Efficacy and safety from ARIEL4, a randomized phase III study. SGO (2021) abstract 11479
https://www.clearityfoundation.org/wp-content/uploads/2021/03/SGO-11479-ARIEL4-Kristeleit.pdf

Oza AM et al. Subgroup analysis of rucaparib versus chemotherapy as treatment for BRCA-mutated, advanced, relapsed ovarian carcinoma: Effect of platinum sensitivity in the randomized, phase 3 study ARIEL4. J Clin Oncol (2021) 39 (suppl 15; abstr 5517)
https://meetinglibrary.asco.org/record/195553/abstract

Oza AM et al. Poster
https://www.clearityfoundation.org/wp-content/uploads/2021/06/ARIEL4-poster-ASCO-2021-scaled.jpeg

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