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Background Denosumab therapy is commonly used for the prevention of skeletal-related events in patients with bone metastasis. However, a common side effect of denosumab is hypocalcemia. Objective The aim of the study is to determine the incidence of hypocalcemia in patients receiving denosumab for prevention of skeletal-related events in bone metastasis and evaluate risk factors for developing hypocalcemia. Methods This was a retrospective medication use evaluation reviewing the incidence of hypocalcemia in patients receiving outpatient denosumab for prevention of skeletal-related events at Yale–New Haven Hospital. Additionally, various risk factors were reviewed to determine their risk of developing hypocalcemia. Results As per Common Terminology Criteria for Adverse Events v4.03, of the 106 patients included in the study population, 37 (35%) patients had an incidence of hypocalcemia within 30 days of denosumab administration. Fourteen patients (13.2%) had an incidence of grade 1, 13 patients (12.3%) had an incidence of grade 2 hypocalcemia, and 7 patients (6.6%) had an incidence of grade 3 hypocalcemia. Grade 4 hypocalcemia occurred in three (2.8%) patients. Calcium supplementation did not decrease the risk of developing hypocalcemia. Patients who had one or more episodes of acute kidney insufficiency were at a higher risk of developing hypocalcemia (odds ratio = 7.5 (95% confidence interval = 1.8–36.3), p = 0.001). Conclusion This study found that the overall incidence of hypocalcemia and severe hypocalcemia was higher than reported in clinical trials. Additionally, calcium supplementation did not have an effect on incidence of hypocalcemia, while patients who experienced acute kidney insufficiency while on denosumab had a higher likelihood of developing hypocalcemia. [ABSTRACT FROM AUTHOR]

Bronchodilators play an important role in the management of stable chronic obstructive pulmonary disease (COPD). Although bronchodilators do not prevent the decline in lung function in patients with COPD, their efficacy in improving disease-related symptoms, reducing the frequency and seventy of disease exacerbations, and improving patients' quality of life has been demonstrated in clinical trials. Arformoterol, the (R,R)-enantiomer of the selective beta2-agonist formoterol, is a potent, highly specific, nebulized long-acting beta2-adrenergic agonist recently approved by FDA for the long-term maintenance treatment of bronchoconstriction in patients with COPD, including chronic bronchitis and emphysema. In 2 large, 12-week, phase 3 studies, arformoterol demonstrated an efficacy superior to that of placebo and comparable to that of salmeterol in patients with COPD. In these trials, arformoterol was well tolerated, with a safety profile similar to that of other inhaled long-acting beta2-agonists when used at the FDA-approved dose. Arformoterol is the only long-acting beta2-adrenergic agonist available as an inhalation solution for use with a nebulizer, thus providing a new option for patients who are unable to use a dry-powder inhaler. Evaluation of the long-term safety and efficacy of arformoterol in patients with COPD is currently under way. INSET: Formulary considerations. [ABSTRACT FROM AUTHOR]

The article provides information on atrasentan, a member of a new class of drugs called the selective endothelin-A receptor antagonists. Endothelin-1, which comes from prostate cancer cells, can stimulate new bone formation and can also act synergistically with a number of growth factors promoting the growth and proliferation of cancer cells. The safety and efficacy of atrasentan in hormone refractory prostate cancer have been evaluated in several clinical trials. Atrasentan demonstrated some efficacy in delaying the progression of disease and improving the quality of life of patients while having an acceptable safety profile. INSET: Formulary considerations.

Purpose Research pharmacy effort required to safely and compliantly manage investigational products (IP) varies between studies. No validated tool exists in the United States to evaluate these differences in effort. The Vizient Pharmacy Research Committee Investigational Drug Services (IDS) Subcommittee previously developed a systematic complexity scoring tool (CST) through expert consensus to assign a complexity score for pharmacy effort. This project seeks to develop and validate complexity categories based on CST scores. Methods Vizient member institutions in IDS assigned a CST complexity score and a perceived complexity category (low, medium, or high) for study initiation and maintenance. Receiver operating characteristic (ROC) curve analysis defined the best CST score cutoff points for each complexity category. Comparing the CST-assigned to the user-perceived complexity category determined whether the CST-assigned complexity category aligned with practitioner assignment. Results A total of 322 responses were used to determine complexity score categories. The AUC values for study initiation and maintenance were 0.79 (P < 0.001) for the low/medium boundary and 0.80 (P < 0.001) for the medium/high boundary, suggesting the performance of the CST is good. The agreement between CST-assigned and user-perceived complexity categories was 60% for study initiation and 58% for maintenance. The Kendall rank correlation coefficient between the raters and ROC categories was strong, with a value of 0.48 for study initiation and 0.47 for maintenance. Conclusion Development of the CST allows IDS pharmacies to objectively measure the complexity of clinical trials, which is a significant step towards assessing workload and guiding resource allocation. [ABSTRACT FROM AUTHOR]

There exists some apprehension by prescribers, healthcare providers, and other stakeholders regarding the real-world safety and effectiveness of biosimilars. While some of the apprehension is likely due to clinician knowledge gaps in the biosimilarity exercise, additional data (including those generated from the real-world) regarding safety and efficacy could reduce a clinician's perception of biosimilar uncertainty and can potentially increase biosimilar acceptance and uptake. The published literature is lacking regarding the real-world impact on healthcare costs and clinical outcomes when a single healthcare institution converts from filgrastim to filgrastim-sndz as its short-acting Granulocyte Colony Stimulating Factor (GCSF), especially within diverse populations and indications not explicitly studied through the registration trials. Specifically, both filgrastim and filgrastim-sndz possess FDA-approved indications within patients with hematologic malignancies receiving high-dose chemotherapy and in those undergoing bone marrow transplantation. As a biosimilar to filgrastim, the FDA did not require prospective, randomized controlled trials to obtain these indications for filgrastim-sndz. The purpose of this study is to describe real-world healthcare resource costs, utilization patterns, and clinical outcomes in patients with hematologic malignancies who received filgrastim-sndz or filgrastim to support neutrophil recovery following chemotherapy (i.e., induction or consolidation) or a bone marrow transplant (BMT) at Yale New Haven Hospital (YNHH).A total of 148 patients were identified and met the following criteria: at least 18 years old, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, absence of fever or infection, newly diagnosed acute myeloid leukemia or newly post-bone marrow transplant and received filgrastim-sndz (Zarxio®) or reference filgrastim (Neupogen®).Healthcare resource utilization outcomes were compared between biosimilar and reference filgrastim using descriptive statistics. There were no major differences between either cohort, including duration of hospitalization, the number of overall emergency room visits and additional hospital admissions with a primary diagnosis of febrile neutropenia or neutropenia within 30 days post-discharge from initial hospital admission, time to neutrophil recovery following GCSF support, and the incidence and duration of both fever and febrile neutropenia. The total cost based on treatment of all patients in each arm differed significantly with filgrastim-sndz being the most cost-effective choice.filgrastim-sndz significantly reduced healthcare utilization costs compared to reference filgrastim with similar effect on absolute neutrophil count, incidence of fever, and febrile neutropenia. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors (ICIs) have revolutionized the care of patients with cancer, but use among hospitalized patients is controversial as a result of questionable benefit and high costs. To evaluate the role of ICIs in the inpatient (IP) setting, we conducted the Inpatient Immunotherapy Outcomes Study (IIOS) to describe characteristics and outcomes of patients who received IP ICIs., Methods: IIOS is a retrospective study of patients treated with ICIs during hospitalization between 2012 and 2021 at five academic institutions. Data collection was performed using each institution's electronic medical record. We estimated overall survival (OS) from the first administration of ICI using the Kaplan-Meier method and used adjusted Cox proportional hazards models to explore associations between clinicodemographic variables and OS., Results: Two hundred fifteen patients received IP ICIs (median age 60 years; 55% White; 14% Black; 13% Hispanic). Thoracic and head and neck (24%), GI (21%), and hematologic (19%) malignancies were most common. Most of the patients were ICI-naïve (75%), had stage IV solid malignancies (75%) at the time of IP ICI initiation, and had no radiographic response to ICI therapy (88%). Median OS from the first IP ICI dose was 1.55 months (95% CI, 1.08 to 1.81) for all patients and 1.28 months (95% CI, 0.95 to 1.80) for patients with advanced solid malignancies. Multivariable Cox proportional hazards model analysis found no clinicodemographic variables associated with improved OS after IP ICI administration., Conclusion: IIOS is the largest multi-institutional effort to describe outcomes after IP ICI administration. Clinical outcomes are poor after IP ICI use and IP ICIs should be used with caution.

Pancreatic cancer is one of the most devastating solid tumor malignancies. Majority of patients have metastatic disease upon diagnosis. Five-year survival is less than 5% for all stages of pancreatic cancer combined. Gemcitabine has been the standard palliative therapy for advanced pancreatic cancer over the past decade. Many studies attempted to develop combination regimens, but they failed to improve overall survival in the metastatic settings. The combination of gemcitabine and erlotinib was the first combination regimen to show improvements in survival benefit compared with gemcitabine alone and became the first-line combination therapy in advanced pancreatic cancer. The search for better treatment strategies to prolong survival in this deadly disease is very much needed and is a worldwide effort. There were many studies presented at the 2010 American Society of Clinical Oncology (ASCO) Annual Meeting focused on first-line therapy in metastatic pancreatic cancer. This article highlights a few phase III and II studies that have demonstrated encouraging results.