Guidelines for Management of Treatment-Emergent Adverse Events During Rucaparib Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer

Purpose: The US Food and Drug Administration has recently granted accelerated approval of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib as treatment for men with metastatic castration-resistant prostate cancer (mCRPC) associated with a deleterious germline or somatic BRCA1 or BRCA2 (BRCA) alteration. As the safety profile of this new addition to the mCRPC treatment landscape may be unfamiliar to clinicians and patients, we summarize the data from the literature and provide practical guidelines for the management of treatment-emergent adverse events (TEAEs) that may occur during rucaparib treatment.

Materials and methods: Safety data were identified from PubMed and congress publications of trials involving men with mCRPC treated with oral rucaparib monotherapy (600 mg twice daily). Management guidelines for TEAEs were developed based on trial protocols, prescribing information, oncology association guidance, and the authors' clinical experience.

Results: In clinical trials of men with mCRPC who received rucaparib (n = 193), TEAEs observed were consistent with that of other PARP inhibitors. The most frequent any-grade TEAEs included gastrointestinal events, asthenia/fatigue, anemia, increased alanine/aspartate aminotransferase, rash, and thrombocytopenia; the most frequent grade ≥3 TEAE was anemia. The majority of TEAEs were self-limiting and did not require treatment modification or interruption. Here, we provide recommendations on management of the most common TEAEs reported with rucaparib as well as other TEAEs of interest.

Conclusion: Rucaparib's recent approval for treatment of BRCA-mutant mCRPC is practice changing. Proper management of TEAEs will allow maximum treatment benefit for patients receiving rucaparib.