Cost-effectiveness of CDK4/6 inhibitors in HR+/HER2- metastatic breast cancer: a systematic review and meta-analysis.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors have emerged as a significant advancement in the treatment of HR+/HER2- metastatic breast cancer (MBC). Despite the clinical efficacy of CDK 4/6 inhibitors in HR+/HER2- metastatic breast cancer, there remains a significant gap in understanding their cost-effectiveness, particularly regarding the long-term economic impact and the key drivers of costs, when used in combination with endocrine therapy. This study aims to systematically review and conduct a meta-analysis of cost-effectiveness studies evaluating CDK4/6 inhibitors in treatment of HR+/HER2- advanced breast cancer and identify key drivers of costs of CDK4/6 inhibitors in combination with endocrine therapy. METHODS: A comprehensive search of PubMed and Embase was conducted to identify peer-reviewed studies from February 2015 to March 2022 reporting cost-effectiveness of CDK4/6 inhibitors in MBC treatment. Incremental net benefits (INBs) were estimated, and meta-analysis was conducted. This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: We identified 120 articles, of which 18 were eligible for systematic review and 16 for meta-analysis. None of the three CDK4/6 inhibitors had positive INB compared to endocrine/aromatase inhibitors therapy alone. The pooled INB was estimated at -$149,266.87 (95% Confidence Interval (CI) = -$196,961.54, -$101,572.20). CONCLUSION: The combination of CDK4/6 inhibitors and letrozole/endocrine therapy for the treatment of postmenopausal patients with advanced HR+/HER2 - MBC was not cost-effective.

Breast cancer, a significant health concern worldwide, represents around 30% of new cancer diagnoses and 25% of cancer related fatalities. Among these cases, approximately two-thirds are characterized by hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) tumors. In the metastatic stage, up to half of patients exhibit inherent resistance to endocrine therapy, leading to poorer survival rates, while others, initially responsive, eventually develop resistance, leading to disease progression and eventual mortality. Nevertheless, recent advancements in CDK4/6 inhibitors have shown efficacy in overcoming both inherent and acquired endocrine resistance, representing a substantial breakthrough in HR+/HER2− metastatic breast cancer treatment. This study conducts a review of literature focusing on comparative cost-effectiveness and economic evaluations of the three CDK4/6 inhibitors, evaluating the pooled incremental net benefit (INB) reported in these studies. It marks the first attempt to compare all three CDK4/6 inhibitors and employs a meta-analysis approach to ascertain the option demonstrating the most positive INB. Our findings indicate that CDK4/6 inhibitors fail to provide an economic advantage over letrozole or endocrine therapy alone. The aim of this study is to offer insights for clinical and reimbursement decision-making in the treatment of postmenopausal patients with advanced HR+/HER2− breast cancer, providing valuable guidance for policymakers, payers, and clinicians.

The association between toxicity and efficacy of immune checkpoint inhibitors in older adults with NSCLC.

Aim: This cohort study evaluated the association between immune checkpoint inhibitors (ICIs)-induced immune-related adverse events (irAEs) and mortality as well as ICI discontinuation among older adults with NSCLC.Methods: 2007-2019 Surveillance, Epidemiology and End Results-Medicare linked database was used and survival analysis with time-varying exposure of irAEs was applied to estimate the associations.Results & conclusion: A total of 8,175 individuals were included, with 46.8% of whom developed an irAE. Cox regression models showed the occurrence of any irAEs was associated with increased risk of mortality (HR: 1.73, 95% CI: 1.63-1.82) and treatment discontinuation (HR: 1.87, 95% CI: 1.78-1.97). Some variability was observed in the effect on the two outcomes depending on the type of irAE.

A few studies have suggested that certain adverse events related to the immune system (called immune-related adverse events, or irAEs) following treatment of immune checkpoint inhibitors (ICIs) are linked to better clinical outcomes associated with ICI treatment. In contrast, this study of older adults with lung cancer found that patients suffering from irAEs were more likely to die and discontinue ICI treatment. Adverse events such as pneumonitis, arrhythmia, acute kidney injury, hepatitis and colitis were found to be associated with worse outcomes, while hypothyroidism and dermatologic irAEs were not. To prevent life-threatening outcomes for older adults with lung cancer, it is important to closely monitor for the development of irAEs following the initiation of ICI therapy.

Incidence and risk factors of immune-related adverse events induced by immune checkpoint inhibitors among older adults with non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitor (ICI) treatment has been linked to a variety of immune-related adverse events (irAEs), which can affect any organ system. The incidence and risk factors of irAEs have not been adequately evaluated among older adults with NSCLC. METHODS: A cohort study was conducted using 1999-2019 SEER-Medicare data among beneficiaries aged ≥65 years with a diagnosis of NSCLC who received nivolumab, pembrolizumab, or atezolizumab. Incident irAEs were identified post-ICI initiation. Demographic, cancer-related characteristics, and clinical history risk factors of irAEs were evaluated with competing events considered. RESULTS: A total of 8175 older NSCLC patients were included (with 46.8% experiencing irAEs). Pneumonitis (16.5%), hypothyroidism (10.5%), arrhythmia (11.18%), and acute kidney injury (AKI) (5.8%) were the most common irAEs. The median time to first irAE was 82 days (IQR: 29-182 days). The earliest onset of irAE occurrence was for hematologic irAEs, while the latest were gastrointestinal, dermatologic, and musculoskeletal irAEs. Fine-Gray regression modeling revealed significantly greater hazards of irAE occurrence in patients who received pembrolizumab at index, did not have CNS metastases, had a history of autoimmune disorder, and had chemotherapy in combination with ICI. Race, socioeconomic status, previous radiation therapy, and comorbidity burden were found to be associated with the occurrence of certain type of irAEs. CONCLUSION: A significant proportion of older patients with NSCLC develop an irAE after receiving ICI treatment. Factors related to cancer and treatment as well as demographics contribute to the increased risk of irAEs. Close monitoring and prediction of irAE among older patients receiving ICI is warranted.

Interprofessional education tracks: One schools response to common IPE barriers.

BACKGROUND: Implementing meaningful interprofessional education (IPE) experiences into the curriculum often requires overcoming barriers and challenges. To overcome these challenges on a non-medical center campus, school of pharmacy IPE faculty implemented a longitudinal, three-semester, multi-track series. The goals of forming a multi-track series were: (1) to overcome the pharmacy class size compared to the other available disciplines, (2) to utilize disciplines available on a liberal arts campus, and (3) to address varying academic calendars between disciplines. INTERPROFESSIONAL ACTIVITY: In 2018, the IPE course series was developed and imbedded within the first- and second-year, required, one-credit hour IPE courses. Tracks included community wellness involving accelerated bachelor of science in nursing students on the liberal arts campus, health law involving juris doctorate candidates on the liberal arts campus, and quality management involving masters of science in nursing administration and doctor of medicine students on the medical campus. Each pharmacy student was assigned a track spring semester of the first year based on preference. DISCUSSION: Creation of the track series successfully overcame barriers for IPE implementation. The use of multiple partners, smaller cohorts, and virtual technology allowed faculty greater flexibility, smaller student cohorts, and group autonomy to determine best time and method for meetings, assignment completion, and events. IMPLICATIONS: Utilization of a non-traditional course structure allowed for creative solutions to common barriers related to implementation of IPE on a liberal arts campus. This concept can be applied to a wide variety of curriculums to implement meaningful interprofessional experiences.

Management of venous thromboembolism with non-vitamin K oral anticoagulants: A review for nurse practitioners and pharmacists.

BACKGROUND AND PURPOSE: Venous thromboembolism (VTE), comprising deep-vein thrombosis and pulmonary embolism, is associated with significant morbidity and mortality. Non-vitamin K oral anticoagulants (NOACs), including apixaban, betrixaban, dabigatran, edoxaban, and rivaroxaban, are as effective and safe as vitamin K antagonists (VKAs) for primary prophylaxis, treatment, and/or secondary prevention of VTE and present significant advantages in convenience of use. This review provides guidance to nurse practitioners (NPs) and pharmacists on NOAC usage for the management of VTE and examines how traditional anticoagulation clinics can adapt to cater to patients on NOACs. METHODS: A review of the scientific literature pertaining to treatment guideline recommendations, large randomized clinical trials, and real-world evidence studies related to VTE management was conducted. CONCLUSIONS: With current data suggesting that NOACs may present as better alternatives over VKAs for the management of VTE, comprehensively educating NPs and pharmacists can help incorporate these agents in their clinical practice. IMPLICATIONS FOR PRACTICE: Repurposing anticoagulation clinics, led by well-informed NPs and pharmacists, will allow effective integration and optimal management of patients with VTE taking NOACs as well as those taking VKAs.