PARP (poly-ADP-ribose polymerase) inhibitors are approved for use in BRCA-mutation associated BC and triple-negative BC; the latter is often associated with BRCA1. Two PARP inhibitors are FDA-approved for metastatic, HER2-negative, germline BRCA-mutated BC, olaparib and talazoparib, while two other PARP inhibitors, niraparib and rucaparib, are indicated for ovarian cancer.

A systematic review and meta-analysis was conducted to assess the efficacy and safety of PARP inhibitors in BC compared with chemotherapy. A search was conducted of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from the beginning of the databases to September 21,2020, using the terms “breast cancer” and “PARP inhibitor.”

Articles in the meta-analysis and systematic review had to include randomized, controlled trials with results; studies that used a PARP inhibitor as an intervention and chemotherapy as a control (as monotherapy or combination therapy); and those that conducted statistical analysis on one of the following outcomes: progression-free survival (PFS), overall survival (OS), or overall response rate (ORR).

A total of six studies involving 1,953 patients (1,263 on PARP inhibitors and 690 patients on chemotherapy) were included. These papers focused on the PARP inhibitors olaparib, talazoparib, and veliparib (the latter is not approved for use in the United States). One-third of the studies compared PARP-inhibitor monotherapy to chemotherapy monotherapy; the rest compared combination therapy with a PARP inhibitor and chemotherapy. All studies mentioned BRCA mutation status, with two papers targeting triple-negative BC patients. Two-thirds of studies provided data on the number of patients who had received prior chemotherapy.

PFS was the primary endpoint in five of the six studies, and PARP inhibitors were associated with a 35% improvement (hazard ratio [HR] = 0.65, 95% CI, 0.56-0.74) in this parameter. Significant differences were present in the weighted ORR, but there was much heterogeneity present.

There were no statistically significant differences in treatment discontinuation or necessary dosage adjustments between the PARP inhibitors and chemotherapy. Grade 3 to 4 thrombocytopenia was significantly more common with the PARP inhibitors than with chemotherapy (RR = 1.63, 95% CI, 1.06-2.52; P = .03).

There were significant differences in subgroup analyses between monotherapy and combination therapy in PFS and ORR but not in OS. Monotherapy was associated with a lower risk of disease progression and a higher ORR rate than combination therapy. There was no difference in ORR between those treated with PARP inhibitors and chemotherapy. PFS was not statistically significantly different between BRCA subtypes. PARP inhibitors improved PFS 36% in those BC patients who had not received platinum-based chemotherapy (HR = 0.64, 95% CI, 0.52-0.79).

The authors concluded that PARP inhibitors with or without chemotherapy significantly improved PFS and ORR. However, PARP inhibitors were associated with more severe thrombocytopenia. Patients who would best benefit from these agents include those who have not received previous platinum therapy.

The study helps pharmacists determine the place in therapy of PARP inhibitors in the management of BC patients and supports the close monitoring of patients’ hematological profiles during PARP inhibitor therapy.

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