Olaparib Extends PFS in Relapsed Ovarian Cancer, With Good QOL

Article

Olaparib tablet maintenance therapy provided a significant improvement in progression-free survival over placebo in patients with relapsed, platinum-sensitive ovarian cancer with a BRCA1/2 mutation.

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.

Recent Videos
Oncologists are still working on management strategies for neuropathy; a common adverse effect related to chemotherapeutics for ovarian cancer.
Genetic testing information can be used to risk-stratify ovarian cancer survivors for breast cancer, particularly those with BRCA1 or BRCA2 mutations.
Genetic testing for ovarian cancer may help inform treatment decisions for patients with advanced disease, particularly regarding PARP inhibitor use.
Future findings from a translational analysis of the OVATION-2 trial may corroborate prior clinical data with IMNN-001 in advanced ovarian cancer.
Approximately 10% of patients discontinued treatment with avutometinib/defactinib due to toxicity in the phase 2 RAMP 201 trial.
Response rates appeared to be higher with avutometinib plus defactinib vs avutometinib alone in the phase 2 RAMP 201 study.
Patients who respond to avutometinib/defactinib may be maintained on treatment for long periods of time, says Rachel N. Grisham, MD.
Findings from the OVARIO study show that patients with HRR–deficient and BRCA-mutated disease benefitted the most from niraparib/bevacizumab maintenance.
Related Content