Skip to content
Bending the Curve Trial by Trial
?

ARIEL4

Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial

Phase 3N = 349NCT02855944

Population
Relapsed ovarian carcinoma with a deleterious BRCA1 or BRCA2 mutation and at least two previous chemotherapy regimens
Design
International, open-label, randomised phase 3 trial at 64 sites in 12 countries. Patients with BRCA1- or BRCA2-mutated ovarian carcinoma and at least two previous chemotherapy regimens were randomised 2:1 to rucaparib 600 mg twice daily or chemotherapy chosen by platinum-free interval (weekly paclitaxel for platinum-resistant or partially platinum-sensitive disease; platinum-based chemotherapy for fully platinum-sensitive disease). Primary end point investigator-assessed PFS, in the efficacy population (deleterious BRCA mutation without reversion mutation) and then in the ITT population.
Primary endpoint
PFS
Arms
  • Rucaparib (experimental, n = 233): Rucaparib 600 mg twice daily
  • Chemotherapy (control, n = 116): Weekly paclitaxel, or platinum-based chemotherapy for fully platinum-sensitive disease
People
Kristeleit R
PFSHR 0.64 (95% CI 0.49–0.84)Δ median PFS+1.7 monthsPFSHR 0.67 (95% CI 0.52–0.86)Δ median PFS+1.7 monthsOSHR 1.3 (95% CI 1.0–1.7)Δ median OS−6 months
Show the numbers
Results reported for ARIEL4
EndpointAnalysisRucaparibChemotherapyEffect
PFSEfficacy population: deleterious BRCA1/2 mutation without reversion mutation (rucaparib n=220, chemotherapy n=105)primarymedian follow-up 25 monthsKristeleit 2022median 7.4 months (7.3–9.1)median 5.7 months (5.5–7.3)HR 0.64 (95% CI 0.49–0.84)P=0.0010Investigator-assessed.
PFSITT (rucaparib n=233, chemotherapy n=116)primarymedian follow-up 25 monthsKristeleit 2022median 7.4 months (6.7–7.9)median 5.7 months (5.5–6.7)HR 0.67 (95% CI 0.52–0.86)P=0.0017Investigator-assessed.
OSITT (rucaparib n=233, chemotherapy n=116)finalmedian follow-up 41.2 monthsOza 2025median 19.4 months (15.2–23.6)median 25.4 months (21.4–27.6)HR 1.3 (95% CI 1.0–1.7)P=0.047Final prespecified secondary OS analysis. 80 (69%) of 116 patients in the chemotherapy group crossed over to receive rucaparib; 244 (70%) of 349 patients had died. The abstract draws no conclusion about the cause of the difference.
Results reported for ARIEL4
EndpointAnalysisRucaparibChemotherapyEffect
PFSEfficacy population: deleterious BRCA1/2 mutation without reversion mutation (rucaparib n=220, chemotherapy n=105)primarymedian follow-up 25 monthsKristeleit 2022median 7.4 months (7.3–9.1)median 5.7 months (5.5–7.3)HR 0.64 (95% CI 0.49–0.84)P=0.0010Investigator-assessed.
PFSITT (rucaparib n=233, chemotherapy n=116)primarymedian follow-up 25 monthsKristeleit 2022median 7.4 months (6.7–7.9)median 5.7 months (5.5–6.7)HR 0.67 (95% CI 0.52–0.86)P=0.0017Investigator-assessed.
OSITT (rucaparib n=233, chemotherapy n=116)finalmedian follow-up 41.2 monthsOza 2025median 19.4 months (15.2–23.6)median 25.4 months (21.4–27.6)HR 1.3 (95% CI 1.0–1.7)P=0.047Final prespecified secondary OS analysis. 80 (69%) of 116 patients in the chemotherapy group crossed over to receive rucaparib; 244 (70%) of 349 patients had died. The abstract draws no conclusion about the cause of the difference.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSPFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.640.49–0.84
PFS0.670.52–0.86
OS1.31–1.7
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%051015Months (modelled)
  • Rucaparib (experimental)
  • Chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsRucaparibChemotherapy
0100.0%100.0%
562.6%54.4%
943.0%33.5%
1426.9%18.2%
1916.9%9.9%
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%051015Months (modelled)
  • Rucaparib (experimental)
  • Chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsRucaparibChemotherapy
0100.0%100.0%
562.6%54.4%
943.0%33.5%
1426.9%18.2%
1916.9%9.9%
Primary publication: Kristeleit R, Lisyanskaya A, Fedenko A, Dvorkin M, de Melo AC, Shparyk Y, et al. Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2022;23(4):465-478. PubMedDOI

Appears in

Sources

  1. Kristeleit R, Lisyanskaya A, Fedenko A, Dvorkin M, de Melo AC, Shparyk Y, et al. Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2022;23(4):465-478.

    PubMedDOI

  2. Oza AM, Lisyanskaya A, Fedenko A, de Melo AC, Shparyk Y, Rakhmatullina I, et al. Rucaparib versus chemotherapy for treatment of relapsed ovarian cancer with deleterious BRCA1 or BRCA2 mutation (ARIEL4): final results of an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2025;26(2):249-264.

    PubMedDOI