Efficacy and safety of combination of poly-ADP-ribose polymerase inhibitor (PARPi) and chemotherapy compared with chemotherapy alone in treatment of recurrent ovarian carcinoma: a systematic review.

Abstract

Platinum-based chemotherapy after surgical cytoreduction is the universal treatment for advanced ovarian cancer
(OC), however, about eighty percent of patients experienced relapse and progression-free survival remained poor.
Patients who relapsed within one year of treatment eventually become resistant to second-line chemotherapy. PolyADP-ribose polymerase inhibitors are a novel class of targeted therapy that could overcome these challenges by
augmenting the chemotherapeutic activity of other cytotoxic agents. Cumulative Index to Nursing and Allied
Health Literature (CINHAL), Cochrane, and PubMed databases were searched for potentially relevant primary
publications from 2011 to 2022 reporting on the efficacy and safety of the combination of a PARP inhibitor and
chemotherapy versus chemotherapy in recurrent OC and reviewed. The outcomes of interest assessed qualitatively
were progression-free survival (PFS) and grade 3 or higher adverse events (AEs) as measures of efficacy and
safety respectively. Eight randomized controlled trials (RCTs) were included in the systematic review comprising
3,021 patients evaluated the efficacy and safety of PARP inhibitors: Olaparib, niraparib and veliparib with
combinations of bevacizumab, carboplatin, cisplatin, cediranib, cyclophosphamide, and paclitaxel. 824 patients had
33 BRCA mutations while 1,430 had wild-type BRCA, an allele that confers an increased risk of cancer. Most patients
had platinum-sensitive cancers. There was significant prolongation of PFS with PARP inhibitor and chemotherapy
combination compared to chemotherapy in all included trials except one which combined veliparib with
cyclophosphamide. The prolongation of PFS was more remarkable in patients with BRCA mutation and
occasionally patients with wild-type BRCA. Niraparib and veliparib were notably associated with grade 3 or higher
anaemia, neutropenia, and thrombocytopenia, olaparib caused fatigue and gastrointestinal disturbances while
bevacizumab and cediranib caused hypertension. This review suggested that combined PARP inhibitor and
chemotherapy significantly prolonged progression-free survival especially in patients with BRCA mutation
compared to chemotherapy and the combined therapy is safe.