[How to prevent and manage PARP inhibitor-related hematological toxicities in prostate cancer?]

Poly(ADP-ribose) polymerase inhibitors (PARPi) represent a significant advancement in the management of metastatic castration-resistant prostate cancer (mCRPC), substantially improving patient survival both as monotherapy and in combination with androgen receptor pathway inhibitors (ARPi). However, haematological toxicities, anaemia, thrombocytopenia and neutropenia, may compromise treatment continuity and thereby reduce effectiveness. Findings from phase III clinical trials and real-world studies have provided a more comprehensive understanding of these toxicities. Anaemia is the most common, occurring in 15 to 49% of patients at grade≥3, typically within the first two months of treatment. This frequently results in treatment interruptions (15-26%) and dose reductions (11-46%). Investigations into the underlying pathophysiological mechanisms suggest that PARP-1 and PARP-2 proteins play a crucial role in haematopoiesis. Based on French expert recommendations, developed using a Delphi consensus methodology, practical algorithms have been established for the prevention and management of anaemia, neutropenia and thrombocytopenia. These include pre-therapy assessment, adjustments for patients with pre-existing haematological abnormalities, consideration of specific patient populations, guidance on the frequency and modalities of haematological monitoring, and management strategies for grade 2 and 3 toxicities. Effective multidisciplinary coordination among the oncologist, coordinating and/or advanced practice nurse, and pharmacist, alongside the use of digital tools that facilitate real-time monitoring and information sharing, are key strategies to enhance early detection of toxicities and maintain continuity of treatment.