National Harbor, MD—A randomized clinical trial of olaparib strengthened the PARP (poly ADP-ribose polymerase) inhibitor’s role as maintenance therapy for patients with ovarian cancer and BRCA mutation, demonstrating dramatic improvement in progression-free survival (PFS) versus placebo.
Olaparib maintenance resulted in a median PFS of 19.1 months versus 5.5 months in the placebo group. Analysis of all key secondary end points demonstrated significant advantages in favor of olaparib.
A blinded independent review of PFS yielded an even larger advantage in favor of olaparib, reported Eric Pujade-Lauraine, MD, Université Paris Descartes, AP-HP, Paris, France, at the 2017 Society of Gynecologic Oncology meeting.
“This is the first phase 3 trial of olaparib tablets as maintenance treatment and showed a significant benefit in patients with platinum-sensitive, relapsed ovarian cancer and BRCA1/2 mutation. The PFS benefit was supported by significant improvement in the secondary end points of time to first subsequent therapy or death, second PFS, and time to second subsequent therapy or death,” said Dr Pujade-Lauraine.
He reported findings from the phase 3 SOLO-2 trial. The trial was designed to support the accelerated FDA approval after phase 2 data showed that olaparib maintenance therapy significantly improved PFS in patients with previously treated ovarian cancer. Patients with BRCA mutation–positive disease derived the greatest benefit from olaparib.
Enrollment in SOLO-2 was limited to patients with ovarian cancer and BRCA1/2 mutation, and exposure to at least 2 previous lines of platinum-based chemotherapy. Eligible patients had to attain at least a partial response to the most recent platinum therapy.
Patients were randomized in a 2:1 ratio to olaparib or placebo and were treated continuously until progression or death. As Dr Pujade-Lauraine noted, the trial was the first phase 3 evaluation of a tablet formulation of olaparib, which reduced the pill burden associated with the capsule formation. Patients assigned to olaparib received a dose of 300 mg twice daily.
Data analysis comprised 295 patients. When the trial ended, patients allocated to olaparib had prolongation of PFS by more than 1 year compared with the placebo group. The difference translated into a 70% reduction in the hazard ratio (HR) for progression or death (P <.0001) in favor of olaparib maintenance.
The prespecified independent analysis of PFS yielded an even larger difference in favor of olaparib. Patients assigned to active therapy had a median PFS of 30.2 months versus 5.5 months for placebo, a difference that represented a 75% reduction in the HR (P <.0001).
In general, olaparib was well-tolerated, and adverse events were consistent with previous experience with the drug.
“With the exception of anemia, toxicity was mostly low grade,” said Dr Pujade-Lauraine. “Health-related quality of life was similar between the 2 groups.”
Anemia (all grades) occurred in 43.6% of the olaparib group (including grade ≥3 in 19.5%) versus 8.1% (grade ≥3 in 2.0%) of the placebo group. Rates of neutropenia were 19.5% and 5.1% with olaparib versus 6.1% and 4.0% with placebo; and rates of thrombocytopenia were 13.8% and 1.0% with olaparib versus 3.0% and 1.0% with placebo.
The most common nonhematologic adverse events (all grades) with olaparib were nausea, fatigue/asthenia, vomiting, diarrhea, dysgeusia, headache, abdominal pain, decreased appetite, and constipation.
