Challenges in PARP inhibitor therapy: A case of Olaparib-induced liver injury and successful rechallenge with Niraparib.

Olaparib, the first-in-class poly ADP-ribose polymerase (PARP) inhibitor, is approved for first line maintenance treatment in platinum-sensitive FIGO stage 3 and 4 high grade serous ovarian cancer (HGSOC) associated with a deleterious BRCA mutation. We report a case involving a 70-year-old female who experienced significant CTCAE Grade 4 hepatocellular injury after initiating first line maintenance Olaparib for Stage 3C HGSOC. Her liver injury resolved upon discontinuation of Olaparib but promptly recurred upon rechallenge. Extensive investigations, including abdominal ultrasound, computed tomography, and assessments for infectious, metabolic, and autoimmune aetiologies of liver injury, were unremarkable. Her liver enzymes returned to baseline after discontinuing Olaparib once again. Subsequently, the patient was started on Niraparib for maintenance therapy, which she tolerated well. This case represents the first instance of positive rechallenge following Olaparib-induced liver injury and highlights the absence of cross-reactive hepatotoxicity between PARP inhibitors.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: YD has received institutional research funding and honorarium for advisory boards, scientific symposia and educational events from GSK. YD has received honorarium for advisory boards, scientific symposia and educational events from AstraZeneca. KZ and SJ have no conflict of interest to declare.
(© 2024 The Authors. Published by Elsevier Inc.)