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.
Highlights
Ovarian cancer is the most lethal gynecological malignancy [1, 2]
We found that Poly(adenosine diphosphate–ribose) polymerase inhibitors (PARPi) improved progression-free survival (PFS) in both groups (65 years: HR, 0.61; 95% CI, 0.45–0.83; P = 0.002)
We performed subgroup analysis based on the timing of chemotherapy in relation to surgery, and we found that PARPi improved PFS in both the interval surgery group (HR, 0.61; 95% CI, 0.50–0.74; P < 0.001) and the primary surgery group (HR, 0.70; 95% CI, 0.57–0.86; P < 0.001)
Summary
Ovarian cancer is the most lethal gynecological malignancy [1, 2]. There were ∼22,000 new cases and 14,000 deaths due to ovarian cancer during 2019 in the United States [3]. Targeted therapies are a new treatment option for patients with ovarian cancer [7]. Poly(adenosine diphosphate–ribose) polymerase inhibitors (PARPi) including niraparib, rucaparib, and olaparib have been approved as maintenance therapies for relapsed platinumsensitive ovarian cancer patients regardless of BRCA status [10]. It is unclear if PARPi can improve the prognosis of patients with newly diagnosed advanced ovarian cancer. 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
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