Abstract
ObjectivesThough it is known to all that PARP inhibitors (PARPis) are effective when used as maintenance alone for women with recurrent ovarian cancer (ROC), little is known about whether using them in combination with other drugs would contribute to a better efficacy. We performed a systematic review and meta-analysis to explore the efficacy and safety of PARPi combination therapy compared with monotherapy.Materials and MethodsWe searched for randomized controlled trials (RCTs) that offered the date we needed in PubMed, Embase, Cochrane, and major conference. Data extraction and processing were completed by three investigators to compare OS, PFS, and ORR both in intervention and in control subset. Then, we calculated the pooled RR and 95% CI of all-grade and high-grade adverse effects to study its safety. And we evaluated the within-study heterogeneity by using subgroup and sensitivity analysis.Results and ConclusionA total of three eligible RCTs covering 343 women were included. In PFS analysis, PARP inhibitor (PARPi) combination therapy can significantly improve PFS for women with ROC when compared with the controls (HR: 0.46, 95% CI: 0.35 to 0.59), especially for those with mutated BRCA (HR: 0.29, 95% CI: 0.19 to 0.45). And in OS analysis, combination therapy is not inferior to monotherapy (HR: 0.90, 95% CI: 0.50 to 1.61). As for ORR, the effectiveness of combination therapy and monotherapy was almost the same (RR: 1.04, 95% CI: 0.82 to 1.31). Additionally, combination therapy seldom causes more adverse events, both in all-grade and in high grade.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, International Prospective Register of Systematic Reviews (PROSPERO) (identifier, CRD42018109933).
Highlights
Ovarian cancer (OC), with poor prognosis, is one of the most prevalent gynecologic malignancies
In progression‐free survival (PFS) analysis, Poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) combination therapy can significantly improve PFS for women with recurrent ovarian cancer (ROC) when compared with the controls (HR: 0.46, 95% credible interval (CI): 0.35 to 0.59), especially for those with mutated BRCA (HR: 0.29, 95% CI: 0.19 to 0.45)
Studies meeting all of the following criteria were included: [1] Randomized controlled phase II or III trials in women who were histologically or cytologically diagnosed with OC before and had relapsed after initial cure; [2] In intervention group, women were treated with PARPi in combination with chemotherapy, other targeted agents, or immune-oncology agents and so on; [3] Patients were treated with control regimen including chemotherapy, other targeted agents, or immune-oncology agents and so on in monotherapy; [4] Studies own data available for hazard ratio (HR) and 95% credible interval (CI) of progression‐free survival (PFS) or overall survival (OS)
Summary
Ovarian cancer (OC), with poor prognosis, is one of the most prevalent gynecologic malignancies. While cytoreductive surgery combined with platinum-based chemotherapy is usually used for advanced OC [2], despite short-time effect, there are still about 70% of patients suffering from the recurrence after firstline treatment [3], which seriously affects one’s survival time [4]. If the disease recurs 6 months or longer after first-line treatment, further platinum-based therapy and debulking surgery are widely used at first relapse. Chemotherapy will produce chemotherapy-related side effects in patients, and those patients will become treatment-resistant, succumbing to disease [5]. Since cumulative myelosuppression, neurotoxicity, and allergy to platinum-based therapy can be limiting factors in patients receiving multiple lines of treatment [6], new effective therapeutic strategies are needed
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