Olaparib tablet maintenance therapy provided a significant improvement in progression-free survival (PFS) over placebo in patients with relapsed, platinum-sensitive ovarian cancer with a BRCA1/2 mutation, according to a new phase III trial. Toxicity was generally manageable with the therapy.
Though advanced ovarian cancer patients often respond well to first-line chemotherapy, subsequent lines of therapy after recurrence have less and less beneficial effect. “A substantial unmet need exists for well tolerated therapies that can improve long-term disease control in patients with recurrent ovarian cancer,” wrote study authors led by Eric Pujade-Lauraine, MD, PhD, of Université Paris Descartes in France.
The PARP inhibitor olaparib has shown promise in phase II all-comer studies of relapsed ovarian cancer. The new study aimed to confirm this in a phase III setting of relapsed ovarian cancer with BRCA1 or BRCA2 mutations. It included 295 patients, randomized to either olaparib (196 patients) or placebo (99 patients); all had received at least two lines of previous chemotherapy. The study was published online ahead of print in Lancet Oncology.
After a median follow-up of approximately 22 months, the investigator-assessed PFS was 19.1 months with olaparib and 5.5 months with placebo, for a hazard ratio (HR) of 0.30 (95% CI, 0.22–0.41; P < .0001). The 12-month PFS rate was 65% with the study drug, and 21% with placebo. At 24 months, these rates were 43% and 15%, respectively.
The median time to first subsequent therapy was 27.9 months with olaparib and 7.1 months with placebo. The median time to progression was not reached in the olaparib group, while it was 18.4 months in the placebo group. Overall survival data was not yet mature, but as of this analysis there was no difference between the groups, with an HR of 0.80 (95% CI, 0.50–1.31; P = .43).
Measures of quality of life, based on the FACT-O assessment, were no different between olaparib and placebo.
The overall incidence of grade 3–5 adverse events (AEs) in the study was low. The most common grade 3 or worse AE with olaparib was anemia (18% grade 3, 1% grade 4, vs 2% and 0% with placebo). Serious AEs were seen in 18% of olaparib and 8% of placebo patients.
“The improvement in PFS seen using the olaparib tablet formulation in this disease setting is compelling because patients were able to maintain a good quality of life while experiencing a delay in disease progression and, therefore, a delay until the symptoms associated with subsequent chemotherapy treatments,” the authors wrote.