Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors as maintenance therapy in women with newly diagnosed ovarian cancer: a systematic review and meta-analysis

Abstract

Purpose: To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy in women with newly diagnosed ovarian cancer, and to explore whether this therapy produces a survival benefit in a subgroup population with specific clinical characteristics.

Methods: We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science and relevant clinical research registry platforms on October 1, 2019, and included randomized controlled trials (RCTs) that compared PARP inhibitors with placebo in women (aged ≥ 18 years) with newly diagnosed epithelial ovarian cancer.

Results: We identified four RCTs with 3,070 participants. Compared with placebo, PARP inhibitor maintenance therapy showed a clinically significant benefit on progression free survival (PFS) in homologous recombination deficiency (HRD) positive population (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.29-0.53). In contrast, no clear differences were identified between the groups in the HRD negative population (HR, 0.83; 95% CI 0.67-1.03). Further, there was no clear difference between the groups in terms of other outcomes (overall survival, health-related quality of life, and adverse events).

Conclusions: PARP inhibitor maintenance therapy significantly prolongs the PFS of patients with newly diagnosed ovarian cancer, especially in HRD positive patients. The diagnostic test used to determine HRD status plays an important role in guiding PARP inhibitor maintenance therapy. Compared with placebo, the effect of PARP inhibitors on ovarian cancer was probably not affected by the International Federation of Gynecology and Obstetrics stage status, response to first-line chemotherapy, and residual macroscopic disease after debulking surgery.

Keywords: Meta-analysis; Newly diagnosed ovarian cancer; Poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors; Systematic review.

Fig. 1

Study flow diagram

Fig. 2

Subgroup analysis for comparison of PFS between PARPi and placebo. PFS progression free survival, PARPi poly (adenosine diphosphate [ADP]–ribose) polymerase inhibitors, BRCAm Breast cancer gene mutation, HRD Homologous recombination deficiencie

Fig. 3

Subgroup analysis for comparison of PFS between PARPi and placebo. PFS progression free survival, PARPi poly (adenosine diphosphate [ADP]–ribose) polymerase inhibitors, FIGO International Federation of Gynecology and Obstetrics, CR complete response, PR partial response, HR hazard ratio. Note: Bevacizumab combined use in both olaparib and placebo groups in PAOLA-1 trial. Chemotherapy combined use in both veliparib and placebo groups in VELIA trial

Fig. 4

Comparison of AEs between PARPi and placebo in each included study. AEs adverse events, PARPi poly (adenosine diphosphate [ADP]–ribose) polymerase inhibitors; RR risk ratio. Note: Bevacizumab combined use in both olaparib and placebo groups in PAOLA-1 trial. Chemotherapy combined use in both veliparib and placebo groups in VELIA trial