Despite improvements in treatment of advanced recurrent ovarian cancer, less than half of newly diagnosed patients with this disease survive more than 5 years, while relapse rates remain high. The first-line treatment setting provides the most favorable opportunity to improve chances for survival.
SOLO1 was an international, randomized, double-blind, phase 3 trial investigating the efficacy and safety of olaparib versus placebo as maintenance therapy in women with newly diagnosed high-grade serous or endometrioid ovarian cancer with a BRCA mutation who had experienced complete or partial response to prior platinum-based therapy. The study randomized 391 patients in a ratio of 2:1 to receive either olaparib 300 mg twice daily (n = 260) or placebo (n = 131) for up to 2 years or until progression, with median treatment duration of 24.6 months versus 13.9 months, respectively. The primary end point was progression-free survival (PFS). The results of the primary analysis of SOLO1 found that maintenance olaparib reduced the risk of disease progression by 70% compared with placebo (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.23-0.41). The median PFS was not reached in the olaparib arm and was 13.8 months in the placebo arm.
A 5-year follow-up found that the PFS benefit of maintenance olaparib continued beyond the end of the treatment period. Maintenance olaparib was associated with a 67% reduction in PFS (HR, 0.33; 95% CI, 0.25-0.43). The median PFS was 56 months in the olaparib arm versus 13.8 months in the placebo arm, a difference of 42 months. At 5 years, 48% of patients taking olaparib were free from progression and death versus 21% of those taking placebo. In a post-hoc analysis, investigators also examined recurrence-free survival (RFS) in a subgroup of patients (n = 189 olaparib; n = 101 placebo) who were in complete response to platinum-based therapy at baseline. At the 5-year follow-up time point, 52% of patients in the maintenance olaparib arm versus 22% of patients in the placebo arm remained free from relapse or death. The median RFS was not reached in the olaparib arm and was 15.3 months in the placebo arm (HR, 0.37; 95% CI, 0.27-0.52).
In the overall patient population, the patients receiving maintenance olaparib experienced significant improvements versus placebo in time to second objective disease progression (64% vs 41% event-free at 5 years, respectively) and time to initiation of second subsequent treatment (62% vs 35% event-free at 5 years, respectively). Similarly, in the subgroup of patients who were in complete response at baseline, the patients receiving maintenance olaparib experienced significant improvements in time to second objective disease progression versus placebo (68% vs 44% event-free at 5 years, respectively) and time to initiation of second subsequent treatment (65% vs 39% event-free at 5 years, respectively).
The 5-year follow-up safety profile data remained consistent with the previously reported SOLO1 primary findings. The incidence of grade ≥3 adverse events in the overall study population was 40% for maintenance olaparib and 19% for placebo. Adverse events leading to treatment discontinuation were 30% and 4% for olaparib and placebo, respectively. The prolonged follow-up did not reveal any new safety signals or any new cases of myelodysplastic syndrome or acute myeloid leukemia.
The investigators concluded that maintenance olaparib accords significant benefits over placebo with regard to both PFS and RFS, which extend well beyond the end of treatment for patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation.
Abstract and Oral Presentation 811MO. ESMO 2020. September 19-21, 2020. Maintenance olaparib for patients (pts) with newly diagnosed, advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): 5-year (y) follow-up (f/u) from SOLO1.