Two phase 3 trials, namely PAOLA-1 and SOLO-1, have demonstrated the clinical efficacy of olaparib, with or without bevacizumab, in patients with homologous recombination deficiency (HRD)-positive or breast cancer gene (BRCA)-mutated advanced ovarian cancer (OC), leading to regulatory approval across multiple countries.¹ In the latest long-term follow-up of the 2 trials, olaparib monotherapy and in combination with bevacizumab demonstrated clinically meaningful improvement in overall survival (OS) among the patients, consolidating its role as a first-line maintenance therapy in HRD-positive or BRCA-mutated advanced OC.¹

OC is one of the most common cancers among women worldwide and has the highest mortality rate among gynecologic cancers, with a 5-year survival rate of merely 30%-50% in newly diagnosed patients.² The presence of mutations in BRCA1 and BRCA2 were associated with an increased risk of developing OC by 15%-45% and 10%-20%, respectively.³ About 50% of advanced OC patients are HRD-positive, encompassing a wide range of genetic abnormalities, including BRCA mutations.⁴ The current management approach is the adoption of drug treatments, such as olaparib monotherapy or olaparib in combination with bevacizumab, to delay disease progression so as to achieve long-term remission among patients.¹

SOLO-1 was a phase 3 randomized, double-blinded, placebo-controlled, multicenter trial that assessed the efficacy and safety of olaparib as a maintenance monotherapy compared with placebo in newly-diagnosed patients with advanced BRCA-mutated OC following platinum-based chemotherapy.^1,5 The study enrolled 391 eligible patients who were randomized 2:1 to receive olaparib or placebo for 24 months or until disease progression.⁵ The primary study endpoint was progression-free survival (PFS), which was significantly improved with olaparib vs. placebo (HR=0.30; 95% CI: 0.23-0.41; p<0.001).⁵ The prespecified descriptive OS analysis was planned 7 years after randomization of the last patient.¹

In the long-term OS analysis of SOLO-1, the 7-year OS rate with olaparib monotherapy was 67.0% vs. 46.5% with the placebo arm.¹ The olaparib monotherapy significantly reduced the risk of death by 45% vs. placebo (HR=0.55; 95% CI: 0.40-0.76; p=0.0004).¹ In addition, olaparib also significantly prolonged the time to the first subsequent therapy (TFST), with a median TFST of 64.0 months in the olaparib group vs. 15.1 months in the placebo group (HR=0.37; 95% CI: 0.28-0.48).¹

PAOLA-1 was a double-blinded phase 3 trial that evaluated the efficacy and safety of olaparib in combination with bevacizumab vs. bevacizumab alone as a first-line maintenance treatment for newly diagnosed advanced OC patients. The study recruited a total of 806 patients who were randomized 2:1 to receive olaparib + bevacizumab or placebo + bevacizumab.^1,6 The primary endpoint was PFS, which was met in the intention-to-treat (ITT) population with a median follow-up of 22.1 months for olaparib/ bevacizumab (HR=0.59; 95% CI: 0.49-0.72; p<0.001).^1,6

In the 5-year OS analysis of PAOLA-1, olaparib-bevacizumab achieved a median OS of 56.5 months and a 5-year OS rate of 47.3%, which did not differ significantly with the placebo group (median OS=51.6 months; 5-year OS rate=41.5%).¹ In other words, no significant difference in OS was observed with the olaparib-bevacizumab group vs. the placebo-bevacizumab group in the overall population (HR=0.92; 95% CI: 0.76-1.12; p=0.4118).¹ However, the olaparib-bevacizumab regimen showed greater OS benefits among the subgroup of patients who were HRD-positive, with a median OS of 75.2 months vs. 57.3 months in the placebo group (HR=0.62; 95% CI: 0.45-0.85).¹ The 5-year OS rate was also higher at 65.5% among this group of patients in the olaparib-bevacizumab arm vs. 48.4% in the placebo-bevacizumab arm.¹

In both studies, the rates of treatment-emergent adverse events (TEAEs) with olaparib, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), were comparable between the primary PFS analyses and the long-term OS analyses.¹ No new safety signals were identified.¹

In summary, the positive long-term OS results of PAOLA-1 and SOLO-1 pointed to the consolidation of the role of olaparib, with or without bevacizumab, as a first-line maintenance treatment for HRD-positive or BRCA-mutated advanced OC.^1,5,6