Between August 2008 and Feb 2010, 136 patients were randomised to receive olaparib 400 mg orally twice daily, for 28 day cycles, and 129 patients were randomised to receive placebo.r
The primary end point was progression-free survival (PFS) and secondary end points were time-to-progression (TTP), overall survival (OS), objective response rate, disease-control rate, health-related quality of life and safety and tolerability.
Olaparib leads to a clinically significant increase in PFS in patients with platinum-sensitive recurrent serous ovarian cancer. The benefit is greatest in those with a BRCA 1 or 2 (gBRCA) mutation. There was no significant benefit in overall survival.
51% of the overall study population had a germline BRCA (gBRCA) mutation. After a median follow up of 37 months, the median PFS was 11.2 months in the olaparib group with a gBRCA mutation vs 4.3 months in the placebo group with a gBRCA mutation (HR=0.18; 95% CI 0.10 to 0.31; p<0.0001). In patients with wild-type BRCA, the PFS was 7.4 months in the olaparib group vs 5.5 months in the placebo group (HR=0.54; 95% CI 0.34 to 0.85; p=0.0075).r
After median follow-up for overall survival of 71 months, there was no significant benefit in overall survival between groups, even in the subset of patients with BRCA mutations (HR 0.62 [95% CI 0.41 to 0.94]; nominal p=0.025; which did not meet required threshold of p<0.0095 for statistical significance).r
Progression-free survival in all patients and according to BRCA mutation statusr
Legend: NC=not calculable. PFS=progression-free survival. *Wild-type BRCA includes patients with no known BRCA mutation and those with a BRCA mutation of unknown significance
The Lancet Oncology © 2014.
Overall survival in all patients and according to BRCA mutation statusr
(A) All patients (n=265). (B) Patients with BRCAm (n=136). (C) Patients with BRCAwt (n=118). OS=overall survival.
The Lancet Oncology © 2016
There was no statistically significant difference between treatment arms in regards to health-related quality of life (HR-QOL).r There was no data available on the compliance rate for completion of QOL data.