BACKGROUND: Olaparib is a poly(ADP-ribose) polymerase inhibitor and cediranib is 
an anti-angiogenic agent with activity against VEGF receptor (VEGFR) 1, VEGFR2, 
and VEGFR3. Both oral agents have antitumour activity in women with recurrent 
ovarian cancer, and their combination was active and had manageable toxicities 
in a phase 1 trial. We investigated whether this combination could improve 
progression-free survival (PFS) compared with olaparib monotherapy in women with 
recurrent platinum-sensitive ovarian cancer.
METHODS: In our randomised, open-label, phase 2 study, we recruited women (aged 
≥18 years) who had measurable platinum-sensitive, relapsed, high-grade serous or 
endometrioid ovarian, fallopian tube, or primary peritoneal cancer, or those 
with deleterious germline BRCA1/2 mutations from nine participating US academic 
medical centres. We randomly allocated participants (1:1) according to permuted 
blocks, stratified by germline BRCA status and previous anti-angiogenic therapy, 
to receive olaparib capsules 400 mg twice daily or the combination at the 
recommended phase 2 dose of cediranib 30 mg daily and olaparib capsules 200 mg 
twice daily. The primary endpoint was progression-free survival analysed in the 
intention-to-treat population. The phase 2 trial is no longer accruing patients. 
An interim analysis was conducted in November, 2013, after 50% of expected 
events had occurred and efficacy results were unmasked. The primary analysis was 
performed on March 31, 2014, after 47 events (66% of those expected). The trial 
is registered with ClinicalTrials.gov, number NCT01116648.
FINDINGS: Between Oct 26, 2011, and June 3, 2013, we randomly allocated 46 women 
to receive olaparib alone and 44 to receive the combination of olaparib and 
cediranib. Median PFS was 17·7 months (95% CI 14·7-not reached) for the women 
treated with cediranib plus olaparib compared with 9·0 months (95% CI 5·7-16·5) 
for those treated with olaparib monotherapy (hazard ratio 0·42, 95% CI 
0·23-0·76; p=0·005). Grade 3 and 4 adverse events were more common with 
combination therapy than with monotherapy, including fatigue (12 patients in the 
cediranib plus olaparib group vs five patients in the olaparib monotherapy 
group), diarrhoea (ten vs none), and hypertension (18 vs none).
INTERPRETATION: Cediranib plus olaparib seems to improve PFS in women with 
recurrent platinum-sensitive high-grade serous or endometrioid ovarian cancer, 
and warrants study in a phase 3 trial. The side-effect profile suggests such 
investigations should include assessments of quality of life and 
patient-reported outcomes to understand the effects of a continuing oral regimen 
with that of intermittent chemotherapy.
FUNDING: American Recovery and Reinvestment Act grant from the National 
Institutes of Health (NIH) (3 U01 CA062490-16S2); Intramural Program of the 
Center for Cancer Research; and the Division of Cancer Treatment and Diagnosis, 
National Cancer Institute, NIH.