BACKGROUND: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer 
activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high 
percentage of genome-wide loss of heterozygosity. In this trial we assessed 
rucaparib versus placebo after response to second-line or later platinum-based 
chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian 
carcinoma.
METHODS: In this randomised, double-blind, placebo-controlled, phase 3 trial, we 
recruited patients from 87 hospitals and cancer centres across 11 countries. 
Eligible patients were aged 18 years or older, had a platinum-sensitive, 
high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube 
carcinoma, had received at least two previous platinum-based chemotherapy 
regimens, had achieved complete or partial response to their last platinum-based 
regimen, had a cancer antigen 125 concentration of less than the upper limit of 
normal, had a performance status of 0-1, and had adequate organ function. 
Patients were ineligible if they had symptomatic or untreated central nervous 
system metastases, had received anticancer therapy 14 days or fewer before 
starting the study, or had received previous treatment with a poly(ADP-ribose) 
polymerase inhibitor. We randomly allocated patients 2:1 to receive oral 
rucaparib 600 mg twice daily or placebo in 28 day cycles using a 
computer-generated sequence (block size of six, stratified by homologous 
recombination repair gene mutation status, progression-free interval after the 
penultimate platinum-based regimen, and best response to the most recent 
platinum-based regimen). Patients, investigators, site staff, assessors, and the 
funder were masked to assignments. The primary outcome was investigator-assessed 
progression-free survival evaluated with use of an ordered step-down procedure 
for three nested cohorts: patients with BRCA mutations (carcinoma associated 
with deleterious germline or somatic BRCA mutations), patients with homologous 
recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of 
heterozygosity), and the intention-to-treat population, assessed at screening 
and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, 
number NCT01968213; enrolment is complete.
FINDINGS: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 
patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median 
progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 
months (95% CI 13·4-22·9; 130 [35%] patients) in the rucaparib group versus 5·4 
months (3·4-6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% 
CI 0·16-0·34]; p<0·0001). In patients with a homologous recombination deficient 
carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9-16·2) versus 5·4 
months (5·1-5·6; 0·32 [0·24-0·42]; p<0·0001). In the intention-to-treat 
population, it was 10·8 months (8·3-11·4) versus 5·4 months (5·3-5·5; 0·36 
[0·30-0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher 
in the safety population (372 [99%] patients in the rucaparib group vs 189 
[100%] in the placebo group) were reported in 209 (56%) patients in the 
rucaparib group versus 28 (15%) in the placebo group, the most common of which 
were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and 
increased alanine or aspartate aminotransferase concentration (39 [10%] vs 
none).
INTERPRETATION: Across all primary analysis groups, rucaparib significantly 
improved progression-free survival in patients with platinum-sensitive ovarian 
cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 
provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in 
the maintenance treatment setting versus placebo could be considered a new 
standard of care for women with platinum-sensitive ovarian cancer following a 
complete or partial response to second-line or later platinum-based 
chemotherapy.
FUNDING: Clovis Oncology.