Review of drug-drug interactions in patients with prostate cancer.

OBJECTIVE: The objective of this review is to provide an overview of common drug-drug interactions (DDIs) associated with prostate cancer treatments and outline recommendations for managing polypharmacy. DATA SOURCES: A literature search of PubMed, Embase, and CINAHL was carried out to identify pharmacokinetic and pharmacodynamic changes caused by DDIs that are relevant for prostate cancer patients, DDIs between prostate cancer therapies and co-administered medications (both prescription and over-the-counter), and measures to prevent DDIs. Medication package inserts were used to identify the impact of DDI on the prostate cancer therapy and suggested interventions. DATA SUMMARY: No DDIs are expected for the LHRH agonists leuprolide acetate, histrelin, goserelin, or leuprolide mesylate. However, DDIs have been reported for GnRH antagonists, anti-androgens, PARP inhibitors, and taxanes. Although there are no confirmed DDIs for sipuleucel-T to date, it is not generally recommended to use sipuleucel-T concurrently with immunosuppressive medications. Interventions to prevent DDIs include the use of software that can detect clinically significant DDIs, up-to-date medication reconciliation, the inclusion of dedicated clinical pharmacists in cancer treatment teams, and patient/caregiver education. CONCLUSIONS: Prostate cancer patients have a high risk of potential DDIs due to numerous new anti-cancer therapies, the increased use of treatment combinations, and the likelihood of comorbid conditions also requiring drug therapy. Drug-drug interaction screening software, up-to-date medication reconciliation, inclusion of oncology pharmacists on healthcare teams, and patient/caregiver education will aid the development of treatment plans that focus on achieving an optimal risk-benefit profile whilst reducing the risk of DDIs.

Exploration of current pharmacy practice in cardio-oncology: Experiences & perspectives.

INTRODUCTION: Cardiovascular complications can occur in oncology patients secondary to certain cancer therapies. Pharmacists are involved in the care of oncology patients who are at risk of or experiencing cardiotoxicity related to their cancer therapy. Our study aimed to understand how pharmacists in Canada care to these patients and to explore their experiences, perceptions, and challenges. METHODS: Canadian pharmacists currently involved in the care of patients receiving cancer treatments and at risk of or experiencing cardiotoxicity were invited to participate in a 30-min telephone interview using an interview guide. A combination of inductive and deductive reasoning was applied using two coders who independently reviewed the transcribed interviews and identified key concepts and themes. RESULTS: Eight pharmacists were interviewed. Perceived benefits included sharing specialized knowledge and conducting safety assessments. Perceived challenges were the lack of role recognition and resources and fractured continuity of care. Proposed future directions were to play a more substantial role in direct medication management, creation of specific guidance and tools to support the clinical decision-making process, and to understand how pharmacists at other sites were providing care through the creation of a community of practice. CONCLUSIONS: As patient-focused medication specialists, pharmacists help guide clinical decision-making, assess cardiac risk factors, and offer individualized education to meet the holistic needs of oncology patients at risk of or experiencing cardiotoxicities. The creation of a cardio-oncology community of practice may allow pharmacists with a common interest to connect, share learnings, and collaborate on how to continue to advance the delivery of care.

CAR T-cell Therapy for Diffuse Large B-cell Lymphoma in Canada: A Cost-Utility Analysis.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is a novel cell therapy for treating non-Hodgkin lymphoma. The development of CAR T-cell therapy has transformed oncology treatment by offering a potential cure. However, due to the high cost of these therapies, and the large number of eligible patients, decision makers are faced with difficult funding decisions. Our objective was to assess the cost-effectiveness of tisagenlecleucel for adults with relapsed/refractory diffuse large B-cell lymphoma in Canada using updated survival data from the recent JULIET trial. METHODS: We developed an individual-simulated discrete event simulation model to assess the costs and quality-adjusted life-years (QALY) of tisagenlecleucel compared with salvage chemotherapy. Survival estimates were obtained from a published clinical trial and retrospective analysis. If patients remained progression free for 5 y, they were assumed to be in long-term remission. Costing and utility data were obtained from reports and published sources. A Canadian health care payer perspective was used, and outcomes were modeled over a lifetime horizon. Costs and outcomes were discounted at 1.5% annually, with costs reported in 2021 Canadian dollars. A probabilistic analysis was used, and model parameters were varied in 1-way sensitivity analyses and scenario analyses. RESULTS: After we incorporated the latest clinical evidence, tisagenlecleucel led to an additional cost of $503,417 and additional effectiveness of 2.48 QALYs, with an incremental cost-effectiveness ratio of $202,991 compared with salvage chemotherapy. At a willingness-to-pay threshold of $100,000/QALY, tisagenlecleucel had a 0% likelihood of being cost-effective. CONCLUSIONS: At the current drug price, tisagenlecleucel was not found to be a cost-effective option. These results heavily depend on assumptions regarding long-term survival and the price of CAR T. Real-world evidence is needed to reduce uncertainty. HIGHLIGHTS: For patients with diffuse large B-cell lymphoma who failed 2 or more lines of systemic therapy, CAR T was not found to be a cost-effective treatment option at a willingness-to-pay threshold of $100,000.These results heavily depend on the expected long-term survival. The uncertainty in the model may be improved using real-world evidence reported in the future.

Clinical Considerations for the Integration of Adjuvant Olaparib into Practice for Early Breast Cancer: A Canadian Perspective.

With the recent Health Canada approval of olaparib for high-risk, HER2-negative early breast cancer, physicians are now facing the practical challenges of integrating olaparib into current management of triple-negative breast cancer (TNBC) and HR-positive, HER2-negative (HR+/HER2-) early breast cancer. This review provides perspectives on some of the challenges related to identification of olaparib candidates, with a focus on the latest guidance for germline BRCA testing and considerations regarding high-risk disease definitions. Updated treatment pathways are explored for both disease states, including other adjuvant treatment options such as pembrolizumab, capecitabine, and abemaciclib. Gaps in the current literature regarding the sequential or combined use of these adjuvant therapies are noted and future, potentially informative, studies are briefly examined.

Understanding the Feasibility of Implementing CAR T-Cell Therapies from a Canadian Perspective.

In Canada, chimeric antigen receptor (CAR) T-cell therapy was recommended for funding for the treatment of select hematological cancers. Canadian hospitals have limited experience and capacity in administrating this therapy. We conducted a qualitative interview-based study with stakeholders in Canada. Questions were asked related to the development, administration, implementation and logistical planning of CAR T-cell therapy. Results were summarized into four main themes: (i) novel; (ii) patient characteristics and the delivery of care; (iii) processes from "bench-to-bedside"; and (iv) the future state, including both challenges and recommendations to ensure sustainability. Valuable perspectives from stakeholders highlight some of the unique challenges to implementing a highly personalized and expensive-to-deliver therapy.

Impact of Increasing Wait Times on Overall Mortality of Chimeric Antigen Receptor T-Cell Therapy in Large B-Cell Lymphoma: A Discrete Event Simulation Model.

PURPOSE: The development of chimeric antigen receptor (CAR) T cells has transformed oncology treatment, with the potential to cure certain cancers. Although shown to be effective in selected populations and studies, CAR T-cell technology requires considerable health care resources, which may lead to additional wait times to access this type of treatment in future. The objective of our study was to estimate the potential impact of increasing wait times on CAR T-cell therapy effectiveness compared with standard chemotherapy for patients with relapsed/refractory diffuse large B-cell lymphoma. METHODS: A health system-level discrete event simulation model was developed to project the potential impact of wait times on CAR T-cell therapy for patients with relapsed/refractory diffuse large B-cell lymphoma. Waiting queues and health states related to treatment and clinical progression were implemented. Using data from the literature, we evaluated nine scenarios of using CAR T-cell therapy with wait times ranging from 1 to 9 months. The outcome of interest was 1-year all-cause mortality. RESULTS: Increasing the wait time of receiving CAR T-cell therapy from 1 to 9 months increased the predicted 1-year mortality rate from 36.1% to 76.3%. Baseline 1-year mortality was 34.0% in patients receiving CAR T-cell therapy with no wait times and 75.1% in patients treated with chemotherapy. This resulted in an increased relative mortality rate of 6.2% to 124.5% over a 1- to 9-month wait time compared with no wait time. CONCLUSION: We found that modest delays in CAR T-cell therapy significantly hinder its effectiveness. Because CAR T-cell therapy offers a potential cure, it is expected that the uptake rate will be substantially increased once the therapy is regularly funded by a health care system. Wait times may be prolonged if system resource availability does not match the demand. Strategies must be developed to minimize the impact of delays and reduce complications during waiting.

Postmenopausal bleeding due to chronic DIC.

'Bleeding disorders' are listed as a cause of postmenopausal bleeding even though there appear to be no reported cases. We present a case of postmenopausal bleeding, because of chronic DIC, which resulted from aortic aneurysm and was managed with replacement blood products and tranexamic acid.