Peripheral Neuropathy in Patients With Ovarian Cancer Administrating Poly ADP-Ribose Polymerase Inhibitors: A Real-World Study Based on Bayesian Disproportionality Analysis of the US Food and Drug Administration Adverse Event Reporting System

Purpose

The aim of this study was to analyze adverse events in terms of safety signals and conduct pairwise comparisons on the constituent ratios of the reporting rates, severity, and outcomes of peripheral neuropathy among poly ADP-ribose polymerase inhibitors in the treatment of epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer (collectively referred to as EOC) leveraging the US Food and Drug Administration Adverse Event Reporting System.

Methods

Data on peripheral neuropathy reports related to EOC treatment submitted to the US Food and Drug Administration Adverse Event Reporting System from the first quarter of 2015 to the third quarter of 2024 were collected. Three poly ADP-ribose polymerase inhibitors are identified: olaparib, niraparib, and rucaparib. The primary composite end point of this study was the safety signals for peripheral neuropathy in patients with EOC receiving poly ADP-ribose polymerase inhibitors treatment, whereas the secondary end points included the safety signals for sensory neuropathy, autonomic neuropathy, and motor neuropathy. All analyses were conducted using Stata 18.0 MP software.

Findings

A total of 300,810 eligible records were included, among which there were 70,332 reports of peripheral neuropathy. For the primary composite end point, a safety signal related to peripheral neuropathy was detected with niraparib (reporting odds ratio [ROR] = 1.47; information component [IC]₀₂₅ = 0.21), whereas no safety signal was found with olaparib or rucaparib. For the secondary end points, safety signals related to autonomic, sensory, and motor neuropathies were detected with niraparib (ROR = 1.42, IC₀₂₅ = 0.21; ROR = 1.39, IC₀₂₅ = 0.20; ROR = 1.31, IC₀₂₅ = 0.17), whereas no signals were identified with olaparib and rucaparib.

Implications

For patients with EOC, prudent surveillance of peripheral neuropathy is warranted when administrating niraparib. Certainly, more large-scale and long-term follow-up period studies were entailed.