Objective This review will provide an overview of the use rucaparib and olaparib in patients with metastatic castration resistant prostate cancer (mCRPC) with the goal to assist the clinician's decision-making process when considering these agents for an individual patient. Data Sources Searches were conducted in PubMed, relevant meeting abstracts, clinicaltrials.gov, and United States Food and Drug Administration (FDA) documents to identify literature published through July 1, 2021, related to use of rucaparib and olaparib for treatment of prostate cancer. Data Summary In May 2020, the FDA approved rucaparib and olaparib for treatment of mCRPC that is homologous recombination repair (HRR)-deficient. Both agents are approved for previously-treated patients, but there are notable differences in strength of evidence, outcomes studied, required HRR alteration, and required prior therapies. In patients who qualify for therapy, additional factors that may help guide choice of PARP inhibitor include baseline organ function, drug interaction potential, toxicity profiles, and financial factors. Conclusions Rucaparib and olaparib have the potential to improve outcomes for patients with HRR-deficient mCRPC. Differences in strength of evidence and patient- and drug-specific characteristics will assist the clinician when choosing between agents.
Objective: To review published clinical trial data related to efficacy and safety of administering denosumab at extended dosing intervals for prevention of skeletal-related events (SREs) in cancer patients. Data Sources: A literature search of PubMed was performed (January 2006 to February 2023) using the following search terms: denosumab, bone metastasis, bone lesions, and lytic lesions. Abstracts from conferences, article bibliographies, and product monographs were also reviewed. Study Selection and Data Extraction: Relevant English-language studies were considered. Data Synthesis: Early phase II denosumab trials included treatment arms that utilized extended-interval denosumab, and various retrospective reviews, meta-analyses, and prospective trials have included extended-interval regimens. Most recently, the ongoing randomized REDUSE trial is comparing the efficacy and safety of extended-interval denosumab to standard dosing. At this time, the best available data are restricted to small, randomized trials not designed to compare efficacy and safety of extended-interval denosumab to conventional dosing and did not use consistent endpoints. Furthermore, primary endpoints of available trials largely consisted of surrogate markers of efficacy that may not be reflective of clinical outcomes. Relevance to Patient Care and Clinical Practice: Historically, denosumab has been dosed at 4-week intervals for prevention of SREs. If efficacy is maintained, extending the dosing interval could potentially reduce toxicity, drug cost, and clinic visits compared to every 4-week dosing. Conclusions: At this time, data demonstrating efficacy and safety of extended-interval denosumab remain limited, and the results of the REDUSE trial are eagerly anticipated to help answer remaining questions.
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