Pharmacogenomic predictor of long-term residual chemotherapy-induced peripheral neuropathy in ovarian cancer survivors: A substudy of the GINECO Vivrovaire study

With the therapeutic landscape of epithelial ovarian cancer (EOC) rapidly evolving, increased overall survival and a high efficacy of poly ADP ribose polymerase (PARP) inhibitors +/− bevacizumab have been observed, particularly for BRCA-mutated and/or homologous recombination deficiency (HRD) tumors [1,2]. However, carboplatin and paclitaxel continue to be the backbone chemotherapy regimen [3], which is associated with significant long-term toxicity, as demonstrated in the Vivrovaire study [4].

Chemotherapy-induced peripheral neuropathy (CIPN) is highly variable among patients; while some remain asymptomatic throughout treatment, others experience severe neuropathy [5,6]. Mechanisms underlying CIPN remain largely unclear, with no preventive pharmacologic agents being approved presently. No biomarker is also currently available to assess the individual risk of CIPN development. The inherent interindividual variability may partially depend on drug pharmacokinetics, but it remains imperfectly understood [7,8]. Single-nucleotide polymorphisms (SNPs) in genes that regulate chemotherapy metabolism affect the efficacy and toxicity of several anticancer drugs [[9], [10], [11]]. Cytochrome plays a key role in drug metabolism, and SNPs in these genes may increase the CIPN risk in several cancers [12,13]. Similarly, SNPs in genes involved in DNA response may play a role, particularly with cisplatin [14].

Currently, the evolution of neuropathy after treatment in long-surviving patients remains poorly studied; however, neuropathy reportedly persists in many patients and may be a major factor in quality-of-life (QoL) impairment [4,15]. Given the increased probability of cure in some EOC subgroups, the long-term effect of CIPN must be more widely considered. Thus, this study aimed to evaluate CIPN incidence in long-term EOC survivors by using a patient-reported outcome (PRO) tool and determine the pharmacogenomic factors of long-term persistent CIPN.

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