Olaparib blocks repair of single-strand DNA breaks by binding to the active site of DNA-associated PARP, preventing the enzyme’s dissociation from the DNA.
Study 19 was a randomised, double-blind, placebo-controlled phase II trial involving 265 patients with serous ovarian cancer, including fallopian tube or primary peritoneal cancer, who had been treated with at least two platinum-containing regimens. A total of 136 patients were assigned to the olaparib group and received 400mg twice daily; the other 129 received placebo.
Progression-free survival was significantly longer with olaparib than with placebo (median 8.4 months vs 4.8 months; hazard ratio for progression or death 0.35, 95% CI 0.25–0.49, p<0.001). Patients taking olaparib had a lower risk of disease progression regardless of progression-free survival.
In an interim analysis, overall survival did not differ significantly between patients taking olaparib and those taking placebo (p=0.75)
Patients in the olaparib group experienced more side-effects than those in the placebo group, most commonly nausea (68%), fatigue (49%), vomiting (32%) and anaemia (17%).