PARP-inhibitor potpourri: A comparative review of class safety, efficacy, and cost

Abstract

Purpose To summarize similarities and differences in efficacy, safety, and cost of available PARP-inhibitors and offers pearls to distinguish subtle nuances between each agent to help guide therapy. Summary Currently, four PARP-inhibitors (olaparib, rucaparib, niraparib, and talazoparib) are FDA-approved, with olaparib, rucaparib, and niraparib approved for treatment and/or maintenance or ovarian cancer and olaparib and talazoparib approved for the treatment of recurrent metastatic BRCA-mutant, HER2-negative breast cancer. While the PARP-inhibitor class is generally are well-tolerated, each agent does possess a unique side-effect profile. Niraparib and talazoparib have more prominent hematologic adverse event profiles, while niraparib has an increased risk of cardiac events. In patients using other medications with known drug interactions, niraparib may be the preferred option for patients with ovarian cancer, and talazoparib may be the preferred option for patients with breast cancer because neither of these agents undergo hepatic metabolism. These agents also can incur large financial toxicities for patients, and olaparib currently has the broadest range of options for financial assistance. Conclusion Although these agents have similar approved indications, efficacy, and toxicity profiles, there are notable differences that may help direct choice of therapy and optimize treatment for patients. It is important to incorporate patient-specific factors to optimize PARP-inhibitor therapy for patients.

Cost-utility of talazoparib monotherapy treatment for locally advanced or metastatic breast cancer in Spain

“…Further, they are currently being studied and approved in new neoplastic locations, encompassing similar therapeutic breast cancer scenarios to the one studied in the present research. The most significant associated adverse events include haematological complications, which must be kept under observation and managed therapeutically [ 21 ].…”

PARP Inhibitors and Haematological Malignancies—Friend or Foe?

“…Olaparib was associated with the highest risk of neutropaenia [ 150 ] and total grade 3 or greater adverse events [ 145 , 152 ]. Overall, niraparib and talazoparib have more prominent haematological adverse event profiles, rucaparib was associated with major abdominal pain events, olaparib with diarrhoea, and niraparib was also associated with an increased risk of cardiac events [ 156 , 157 ]. Haematological adverse events are linked to the PARPi potency of PARP-1 trapping [ 158 ], which also most likely contributes to their effectiveness for the treatment of haematological malignancies.…”

“…Concerningly, the development of MDS and AML has been observed in patients following treatment with PARPi [ 159 , 162 , 163 ]. However, the incidence of AML/MDS development/death is rare; 0.3% of patients treated with talazoparib developed MDS/AML [ 156 ], the death of 1/298 (0.3%) of patients in a phase II trial was attributed to olaparib-related MDS [ 164 ], 1% of patients developed MDS/AML following olaparib treatment in the SOLO1 trial [ 165 ], 0.8% of patients treated with rucaparib in the ARIEL3 study developed MDS/MDL [ 166 , 167 ], and the overall risk of AML/MDS is 0.9% of all patients treated with niraparib [ 165 ]. A meta-analysis with a total of 3 phase III trials in patients with recurrent ovarian cancer, failed to show any statistically significant increased risk of secondary haematological malignancies with the use of PARPi compared to a placebo control arm (Mantel-Haenzel [MH] risk ratio 1.14, 95% CI 0.42–3.08) [ 168 ].…”

PARP inhibitors and the Kidney

“…17 PARP inhibitors can be used as monotherapy or in combination with VEGF inhibitors, checkpoint inhibitors and other novel therapies. 17 The utility of PARPis in the treatment of various malignancies is expected to increase 18 (Table 1).…”