Real-World Delivery of Rucaparib to Patients with Ovarian Cancer: Recommendations Based on an Integrated Safety Analysis of ARIEL2 and Study 10

Abstract

Treatment options for women with recurrent ovarian cancer who have received two or more prior lines of chemotherapy have recently expanded with the U.S. Food and Drug Administration (FDA) and European Commission (EC) approvals of the poly(ADP‐ribose) polymerase (PARP) inhibitor rucaparib. As more oncologists begin to use rucaparib and other PARP inhibitors as part of routine clinical practice, awareness of possible side effects and how to adequately manage toxicities is crucial. In this review, we summarize the safety and tolerability of rucaparib reported in an integrated safety analysis that supported the FDA's initial approval of rucaparib in the treatment setting. Additionally, drawing on clinical data and our personal experience with rucaparib, we provide our recommendations on the management of common side effects observed with rucaparib, including anemia, blood creatinine elevations, alanine aminotransferase and aspartate aminotransferase elevations, thrombocytopenia, gastrointestinal‐related events (e.g., nausea, vomiting), and asthenia and fatigue. These side effects, many of which appear to be class effects of PARP inhibitors, are often self‐limiting and can be managed with adequate interventions such as treatment interruption and/or dose reduction and the use of supportive therapies. Supportive therapies may include blood transfusions for patients with anemia, prophylactic medications to prevent nausea and vomiting, or behavioral interventions to mitigate fatigue. Understanding and appropriate management of potential side effects associated with rucaparib may allow patients with ovarian cancer to continue to benefit from rucaparib treatment. Implications for Practice Rucaparib was recently approved in the U.S. and European Union for use as treatment or maintenance for recurrent ovarian cancer. This review focuses on the safety and tolerability of rucaparib in the treatment setting. Similar side effects are observed in the maintenance setting. Drawing on the authors’ clinical experience with rucaparib, rucaparib prescribing information, and published supportive cancer care guidelines, this review discusses how to optimally manage common rucaparib‐associated side effects in patients with advanced ovarian cancer in the real‐world oncology setting. Adequate management of such side effects is crucial for allowing patients with ovarian cancer to remain on treatment to receive optimal efficacy benefit.

Management of Adverse Events During Rucaparib Treatment for Relapsed Ovarian Cancer: A Review of Published Studies and Practical Guidance

“…In the same analysis, median (95% CI) time to onset of anygrade thrombocytopenia/decreased platelet count was 52 (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57) days, and median (95% CI) time to onset of grade 3 or higher thrombocytopenia/decreased platelet count was 47 (29-63) days [21]. Any-grade neutropenia/decreased neutrophil count was reported in 16.2% of patients in the integrated analysis of safety (median [95% CI] time to onset, 67 In our experience, short-term interruptions in combination with iron and folate supplements are helpful for patients with grade 2 anemia/decreased hemoglobin.…”

“…These AEs may be managed through lifestyle changes, such as taking rucaparib later in the day (e.g. 11:00 am and 11:00 pm vs. 9:00 am and 9:00 pm) [44], eating small, frequent meals, and using natural antiemetics such as ginger (Fig. 2).…”

Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy

“…The most frequently (≥10%) observed any grade adverse reactions in patients receiving rucaparib monotherapy were nausea, fatigue, dysgeusia, anemia, constipation, alanine aminotransferase (ALT) or aspartate aminotransferase (AST), diarrhea, abdominal pain, thrombocytopenia, decreased appetite neutropenia, headache, photosensitivity reactions, cough, dizziness, arthralgia, increase in blood creatinine concentration, dyspepsia [ 76 ].…”

Poly(ADP-ribose) polymerase inhibitors in the treatment landscape of triple-negative breast cancer (TNBC)

“…Rucaparib is associated with elevated ALT, AST, and creatinine, while niraparib has been associated with significant rates of thrombocytopenia and hypertension. 140,141 In a systematic review and metanalysis analyzing PARP inhibitor efficacy, it was noted that there was decreased incidence of leucopenia in patients who received niraparib and rucaparib treatment. 142 Although discontinuation from PARP inhibitors is infrequent, many patients specifically those using rucaparib and niraparib, require dose reductions.…”