Maintenance treatment with oral olaparib in women with BRCA1/2 mutation and relapsed ovarian cancer

Study Methodology

SOLO2/ENGOT-Ov21 was an international multicenter, randomized, placebo-controlled phase III study. It evaluated maintenance therapy with olaparib in patients with relapsed ovarian cancer with a BRCA1/2 mutation who had previously received at least 2 lines of chemotherapy.

Patients were randomly assigned in a 2:1 ratio to receive oral olaparib at a dose of 300 mg twice daily or placebo. A total of 295 patients were enrolled in the study, of whom 196 received maintenance treatment with olaparib and 99 received placebo. Randomization was further stratified based on prior response to chemotherapy (complete or partial) and the duration of the chemotherapy-free interval with a platinum agent (6–12 months vs. >12 months).

The primary endpoint was progression-free survival (PFS), with efficacy analysis performed on the intention-to-treat population (the entire population analyzed based on the originally assigned treatment).

Findings

Efficacy

Progression-free survival (PFS) was significantly longer in patients treated with olaparib (19.1 months; 95% confidence interval [CI] 16.3–25.7) compared to placebo (5.5 months; 95% CI 5.2–5.8), with a hazard ratio (HR) of 0.30 (95% CI 0.22–0.41; p < 0.0001).

Safety Profile

The most common adverse events were anemia, fatigue, or asthenia, with neutropenia also occurring. Serious adverse events were reported in 18% (i.e., 35) of patients receiving olaparib and in 8% of the placebo group. The most common serious adverse events included anemia (7 cases), abdominal pain (3 cases), and intestinal obstruction (3 cases). One patient later developed acute myeloid leukemia.

Conclusion

Maintenance therapy with a PARP inhibitor, a non-classical cytotoxic agent, in women with relapsed ovarian cancer sensitive to prior platinum treatment and positive for the BRCA1/2 mutation resulted in significantly prolonged progression-free survival with acceptable therapy tolerance. Furthermore, olaparib is an oral formulation, contributing to treatment adherence.

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Source: Pujade-Lauraine E., Ledermann J. A., Selle F. et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2mutation (SOLO2/ENGOT-Ov21): a double-blind, randomized, placebo-controlled, phase 3 trial. Lancet Oncol 2017; 18 (9): 1274–1284, doi: 10.1016/S1470-2045(17)30469-2.