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ARIEL3

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Phase 3N = 564NCT01968213

Population
Platinum-sensitive high-grade serous or endometrioid ovarian, primary peritoneal or fallopian-tube carcinoma, at least two prior platinum regimens, in complete or partial response to the last; nested cohorts: BRCA-mutant, HRD (BRCA-mutant or BRCA wild-type with high loss of heterozygosity) and ITT
Design
Randomised, double-blind, placebo-controlled phase 3 trial at 87 sites in 11 countries. Patients with platinum-sensitive high-grade serous or endometrioid ovarian, primary peritoneal or fallopian-tube carcinoma, at least two previous platinum regimens and a complete or partial response to the last, without previous PARP inhibitor treatment, were randomised 2:1 to rucaparib 600 mg twice daily or placebo in 28-day cycles. Primary outcome investigator-assessed PFS in three nested cohorts tested by ordered step-down: BRCA-mutant, HRD and ITT.
Primary endpoint
PFS
Arms
  • Rucaparib (experimental, n = 375): Rucaparib 600 mg twice daily
  • Placebo (control, n = 189): Placebo
People
Coleman RL
PFSHR 0.23 (95% CI 0.16–0.34)Δ median PFS+11.2 monthsPFSHR 0.32 (95% CI 0.24–0.42)Δ median PFS+8.2 monthsPFSHR 0.36 (95% CI 0.30–0.45)Δ median PFS+5.4 months
Show the numbers
Results reported for ARIEL3
EndpointAnalysisRucaparibPlaceboEffect
PFSBRCA-mutant carcinoma (rucaparib n=130, placebo n=66)primaryColeman 2017median 16.6 months (13.4–22.9)median 5.4 months (3.4–6.7)HR 0.23 (95% CI 0.16–0.34)P<0.0001Investigator-assessed; nested cohort within the HRD and ITT populations.
PFSHRD carcinoma (rucaparib n=236, placebo n=118)primaryColeman 2017median 13.6 months (10.9–16.2)median 5.4 months (5.1–5.6)HR 0.32 (95% CI 0.24–0.42)P<0.0001Investigator-assessed; HRD defined as BRCA-mutant or BRCA wild-type with high genome-wide loss of heterozygosity.
PFSITT (rucaparib n=375, placebo n=189)primaryColeman 2017median 10.8 months (8.3–11.4)median 5.4 months (5.3–5.5)HR 0.36 (95% CI 0.30–0.45)P<0.0001Investigator-assessed.
Results reported for ARIEL3
EndpointAnalysisRucaparibPlaceboEffect
PFSBRCA-mutant carcinoma (rucaparib n=130, placebo n=66)primaryColeman 2017median 16.6 months (13.4–22.9)median 5.4 months (3.4–6.7)HR 0.23 (95% CI 0.16–0.34)P<0.0001Investigator-assessed; nested cohort within the HRD and ITT populations.
PFSHRD carcinoma (rucaparib n=236, placebo n=118)primaryColeman 2017median 13.6 months (10.9–16.2)median 5.4 months (5.1–5.6)HR 0.32 (95% CI 0.24–0.42)P<0.0001Investigator-assessed; HRD defined as BRCA-mutant or BRCA wild-type with high genome-wide loss of heterozygosity.
PFSITT (rucaparib n=375, placebo n=189)primaryColeman 2017median 10.8 months (8.3–11.4)median 5.4 months (5.3–5.5)HR 0.36 (95% CI 0.30–0.45)P<0.0001Investigator-assessed.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSPFSPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.230.16–0.34
PFS0.320.24–0.42
PFS0.360.3–0.45
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%010203040Months (modelled)
  • Rucaparib (experimental)
  • Placebo (control)

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

Data table (modelled values)
MonthsRucaparibPlacebo
0100.0%100.0%
1065.9%27.7%
2141.6%6.8%
3127.4%1.9%
4217.3%0.5%
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%051015202530Months (modelled)
  • Rucaparib (experimental)
  • Placebo (control)

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

Data table (modelled values)
MonthsRucaparibPlacebo
0100.0%100.0%
963.2%31.5%
1742.0%11.3%
2626.6%3.6%
3417.7%1.3%
Primary publication: Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, 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. PubMedDOI

Appears in

Sources

  1. Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, 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.

    PubMedDOI