PARP inhibitors (PARPis) are effective treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) as single agents or in combination with androgen receptor-targeted agents (ARTA). However, a clinically relevant adverse effect of these agents is hematological toxicity, a typical class adverse event (AE), which can lead to treatment modifications and discontinuations.
We aimed to analyze the risk of hematological AEs, including anemia, neutropenia, and thrombocytopenia secondary to PARPi treatments in mCRPC.
This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We systematically searched the PubMed, EMBASE, and Cochrane databases, the American Society of Clinical Oncology (ASCO), and the European Society of Medical Oncology (ESMO) meeting abstracts for clinical trials concerning the use of PARPis, both as single agents and in combination, in patients with mCRPC. The search deadline was 30 June, 2023. We analyzed the pooled incidence of all grades of and ≥ G3 anemia, neutropenia, and thrombocytopenia. We subsequently calculated risk ratios (RRs) for all grades of and ≥ G3 AEs of PARPis versus non-PARPis from randomized clinical trials (RCTs).
Eleven phase 2/3 trials with olaparib, niraparib, rucaparib, and talazoparib administered as single agents or combined with ARTA were selected. Anemia was the most common all grades (38.6%) and ≥ G3 AE (24.9%). In the analysis of relative risk, six RCTs were included. The administration of PARPis significantly increased the risk of developing all grades of anemia (RR = 2.44), neutropenia (RR = 3.15), and thrombocytopenia (RR = 4.66) compared with non-PARPis. Similarly, a significant increase in the risk of ≥ G3 anemia (RR = 5.73) and thrombocytopenia (RR = 5.44), and a not significant increased risk of neutropenia (RR = 3.41), were detected.
In mCRPC, PARPis increase the risk of hematological toxicity compared with other treatments, both as single agents or combined with ARTA (high-quality evidence). Clinicians should be aware of this risk and the correct management, especially with the expected increased PARPis use in mCRPC.
Targeted oncology. 2023 Nov 22 [Epub ahead of print]
Brigida Anna Maiorano, Ugo De Giorgi, Elena Verzoni, Evaristo Maiello, Giuseppe Procopio, Vincenza Conteduca, Massimo Di Maio, MeetURO group
Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. ., Department of Medical Oncology, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, Italy., Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy., Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy., Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, Foggia, Italy., Division of Medical Oncology, Department of Oncology, University of Turin, Turin, Italy.