PARP Inhibitors in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Meta-Analysis of Randomized Clinical Trials

Abstract

Background: The efficacy of poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) as a maintenance therapy in patients with newly diagnosed advanced ovarian cancer remains unclear. We conducted a meta-analysis to assess the benefits and safety of PARPi maintenance therapy in patients with newly diagnosed advanced ovarian cancer. Methods: We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs), which assessed the efficacy of PARPi as a maintenance therapy for newly diagnosed advanced ovarian cancer. Progression-free survival (PFS) was the primary endpoint, which was assessed using hazard ratios (HRs) with 95% confidence intervals (95% CI). Progression-free survival was extracted independently, and the pooled results were used to compare the prognoses of patients who received PARPi maintenance therapy and those who received a placebo. Results: Three RCTs, SOLO1, VELIA/GOG-3005, and PRIMA, which included 1,881 patients with newly diagnosed advanced ovarian cancer, were included in the meta-analysis. The overall analysis showed that PARPi maintenance therapy significantly increased PFS (HR, 0.51; 95% CI, 0.33-0.80; P = 0.004) compared to placebo. Subgroup analyses confirmed this result. We also observed an improved PFS in patients with homologous recombination deficiency (HR, 0.50; 95% CI, 0.38-0.66; P < 0.001) and in patients with BRCA mutations (HR, 0.42; 95% CI, 0.31-0.57; P < 0.001). Moreover, there were no significant differences in health-related quality of life between the PARPi and placebo groups. Conclusions: Patients with newly diagnosed advanced ovarian cancer who received PARPi maintenance therapy had a better prognosis than did those who received a placebo. Moreover, no significant changes in health-related quality of life were seen in PARPi-treated individuals.

Keywords: BRCA mutation; PARP inhibitors; homologous recombination deficiency; meta-analysis; newly diagnosed advanced ovarian cancer.

Figure 1

Flow diagram of trial selection.

Figure 2

Risk-of-bias graph.

Figure 3

Progression-free survival (PFS) of all patients.

Figure 4

Progression-free survival (PFS) of (A) subgroups based on age and (B) subgroups based on International Federation of Gynecology and Obstetrics stage.

Figure 5

Progression-free survival (PFS) of (A) subgroup of patients without PARPi in combination with chemotherapy and (B) subgroups based on the timing of chemotherapy in relation to surgery.

Figure 6

Progression-free survival (PFS) of subgroups based on BRCA mutation and homologous recombination status.