Real-World Insights Into Evolocumab Use in Patients With Hyperlipidemia: Canadian Analysis From the ZERBINI Study.

Background: The 2021 Canadian Cardiovascular Society guidelines recommend proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor therapy in patients with atherosclerotic cardiovascular disease whose low-density lipoprotein cholesterol (LDL-C) concentration remains ≥ 1.8 mmol/L despite maximally tolerated statin therapy. This retrospective and prospective observational study characterizes Canadian patients treated with evolocumab and describes its effectiveness and safety.

A retrospective observational study of osteoporosis management after a fragility fracture in primary care.

Unlabelled: In many countries, osteoporosis is predominantly managed by primary care physicians; however, management after a fragility fracture has not been widely investigated. We describe osteoporosis care gaps in a real-world patient cohort. Our findings help inform initiatives to identify and overcome obstacles to effective management of patients after fragility fracture.

Fragility fracture identifies patients at imminent risk for subsequent fracture: real-world retrospective database study in Ontario, Canada.

Background: The secondary fracture prevention gap in the osteoporosis field has been previously described as a 'crisis'. Closing this gap is increasingly important in the context of accumulating evidence showing that an incident fragility fracture is associated with an increased risk of subsequent fracture within 1-2 years, known as imminent fracture risk. The objective of this study was to use health services data to characterize the time between index fragility fractures occurring at different osteoporotic sites and subsequent fractures.

Mortality in older adults following a fragility fracture: real-world retrospective matched-cohort study in Ontario.

Background: Recent studies are lacking reports on mortality after non-hip fractures in adults aged > 65.

Methods: This retrospective, matched-cohort study used de-identified health services data from the publicly funded healthcare system in Ontario, Canada, contained in the ICES Data Repository. Patients aged 66 years and older with an index fragility fracture occurring at any osteoporotic site between 2011 and 2015 were identified from acute hospital admissions, emergency and ambulatory care using International Classification of Diseases (ICD)-10 codes and data were analyzed until 2017.

A Randomized, Single-Blind Study Evaluating the Effect of a Bone Pain Education Video on Reported Bone Pain in Patients with Breast Cancer Receiving Chemotherapy and Pegfilgrastim.

Background: Mild-to-moderate bone pain is the most commonly reported adverse event associated with pegfilgrastim.

Aims: To investigate the effect of bone pain education on pegfilgrastim-related bone pain in patients with breast cancer receiving chemotherapy and pegfilgrastim.

Design: Randomized, single-blind study.

NOLAN: a randomized, phase 2 study to estimate the effect of prophylactic naproxen or loratadine vs no prophylactic treatment on bone pain in patients with early-stage breast cancer receiving chemotherapy and pegfilgrastim.

Purpose: Mild-to-moderate bone pain is a commonly reported adverse event (AE) associated with pegfilgrastim. We evaluated the effect of prophylactic naproxen or loratadine vs no prophylactic treatment on pegfilgrastim-associated bone pain.

Methods: In this open-label study (NCT01712009), women ≥ 18 years of age with newly diagnosed stage I-III breast cancer and an ECOG performance status ≤ 2 who were planning ≥ 4 cycles of adjuvant or neoadjuvant chemotherapy with pegfilgrastim support starting in cycle 1 were randomized 1:1:1 to receive naproxen, loratadine, or no treatment to prevent pegfilgrastim-associated bone pain.

A systematic literature review of the efficacy, effectiveness, and safety of filgrastim.

Purpose: Filgrastim (NEUPOGEN) is the originator recombinant human granulocyte colony-stimulating factor widely used for preventing neutropenia-related infections and mobilizing hematopoietic stem cells. This report presents findings of a systematic literature review and meta-analysis of efficacy and safety of originator filgrastim to update previous reports.

Methods: A literature search of electronic databases, congress abstracts, and bibliographies of recent reviews was conducted to identify English-language reports of clinical trials and observational studies evaluating filgrastim in its US-approved indications up to February 2015.

The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic review.

Purpose: Granulocyte colony-stimulating factors (G-CSF) are commonly used in clinical practice to prevent febrile neutropenia (FN). US and EU prescribing information and treatment guidelines from the NCCN, ASCO, and EORTC specify that pegfilgrastim, a long-acting (LA) G-CSF, should be administered at least 24 h after myelosuppressive chemotherapy. Nevertheless, many patients receive LA G-CSFs on the same day as chemotherapy.

A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pegfilgrastim in Patients Receiving First-Line FOLFOX/Bevacizumab or FOLFIRI/Bevacizumab for Locally Advanced or Metastatic Colorectal Cancer: Final Results of the Pegfilgrastim and Anti-VEGF Evaluation Study (PAVES).

Background: Pegfilgrastim's role in reducing the risk of febrile neutropenia (FN) in patients with colorectal cancer (CRC) receiving chemotherapy plus bevacizumab was not previously evaluated in a prospective study. The present phase III, double-blind trial evaluated the efficacy of pegfilgrastim versus placebo in reducing the incidence of grade 3/4 FN in patients with advanced CRC receiving bevacizumab combined with first-line chemotherapy (FOLFOX [leucovorin, 5-fluorouracil, oxaliplatin] or FOLFIRI [leucovorin, 5-fluorouracil, irinotecan]).

Patients And Methods: Patients aged ≥ 18 years with locally advanced or metastatic CRC were randomized 1:1 to placebo or 6 mg of pegfilgrastim ∼24 hours after receiving chemotherapy plus bevacizumab every 14 days.

Performance of the pegfilgrastim on-body injector as studied with placebo buffer in healthy volunteers.

Objective: The pegfilgrastim on-body injector (OBI) is a single-use, disposable, battery-powered injector that is designed to automatically deliver a single subcutaneous dose of pegfilgrastim beginning approximately 27 hours after activation and continuing over approximately 45 minutes. In this open-label study, we assessed performance of the OBI delivering placebo buffer in healthy volunteers.

Research Design And Methods: Healthy men and women aged 18-55 years, with a body mass index of 18-35 kg/m, were enrolled.

Burden of Chemotherapy-Induced Febrile Neutropenia Hospitalizations in US Clinical Practice, by Use and Patterns of Prophylaxis with Colony-Stimulating Factor.

Introduction: Evidence suggests that many cancer chemotherapy patients who are candidates for colony-stimulating factor (CSF) prophylaxis do not receive it or receive it inconsistent with guidelines, and that such patients have a higher risk of febrile neutropenia hospitalization (FNH). Little is known about the number and consequences of FNH by use/patterns of CSF prophylaxis in US clinical practice.

Methods: A retrospective cohort design and private healthcare claims data were employed.

Relationship between severity and duration of chemotherapy-induced neutropenia and risk of infection among patients with nonmyeloid malignancies.

Purpose: Chemotherapy-induced neutropenia (CIN) may increase infection risk for cancer patients; however, there is limited understanding on the quantitative relationships between severity and duration of CIN and infection risk.

Methods: This study combined individual data from adult cancer patients receiving no granulocyte colony-stimulating factor during the first chemotherapy cycle in six trials. We used area over the curve (AOC) of absolute neutrophil count (ANC) time-response curve (below different thresholds) to measure the combined effect of severity and duration of CIN.

Trajectory of absolute neutrophil counts in patients treated with pegfilgrastim on the day of chemotherapy versus the day after chemotherapy.

Purpose: Risk of infection increases with severity and duration of chemotherapy-induced neutropenia (CIN). Pegfilgrastim is approved for use on the day after chemotherapy to reduce incidence of infection, as manifested by febrile neutropenia (FN), in patients receiving myelosuppressive chemotherapy. In this study, we compared severity and duration of absolute neutrophil count (ANC) suppression in patients who received pegfilgrastim on the same day as chemotherapy versus the next day.

Annual patient and caregiver burden of oncology clinic visits for granulocyte-colony stimulating factor therapy in the US.

Objective: Prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs) is indicated for chemotherapy patients with a significant risk of febrile neutropenia. This study estimates the annual economic burden on patients and caregivers of clinic visits for prophylactic G-CSF injections in the US.

Methods: Annual clinic visits for prophylactic G-CSF injections (all cancers) were estimated from national cancer incidence, chemotherapy treatment and G-CSF utilization data, and G-CSF sales and pricing information.

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis in US clinical practice.

Purpose: Accumulating evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis continue to receive it in subsequent cycles and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Additional evidence from US clinical practice is warranted.

Methods: Data from two US private healthcare claims repositories were employed.

Comorbidities among patients with cancer who do and do not develop febrile neutropenia during the first chemotherapy cycle.

Patients receiving myelosuppressive chemotherapy with certain comorbidities are at increased risk of febrile neutropenia. A comprehensive evaluation of febrile neutropenia-related comorbidities across cancers is needed. This study compared comorbidity prevalence among patients with cancer who did and did not develop febrile neutropenia during the first chemotherapy cycle.

Importance of Risk Factors for Febrile Neutropenia Among Patients Receiving Chemotherapy Regimens Not Classified as High-Risk in Guidelines for Myeloid Growth Factor Use.

Background: Clinical practice guidelines recommend prophylaxis in patients with cancer receiving a colony-stimulating factor (CSF) when the risk of febrile neutropenia (FN) is high (>20%). For patients receiving chemotherapy regimens not documented as high-risk, the decision regarding CSF prophylaxis use can be challenging, because some patients may be at high risk based on a combination of the regimen and individual risk factors.

Methods: A retrospective cohort design and US private health care claims data were used.

A Randomized Trial of Cinacalcet versus Vitamin D Analogs as Monotherapy in Secondary Hyperparathyroidism (PARADIGM).

Background And Objectives: Direct comparison of cinacalcet and vitamin D analogs as monotherapies to lower parathyroid hormone (PTH) levels has not been undertaken.

Design, Setting, Participants, & Measurements: This was a prospective, multicenter, phase 4, randomized, open-label study that enrolled participants from 2010 to 2012. Adult participants (n=312) on hemodialysis with PTH >450 pg/ml were randomized 1:1 to 12 months of treatment with either cinacalcet (n=155) or vitamin D analogs (n=157) to evaluate the mean percentage change in plasma PTH level (primary end point) and the proportion of participants achieving plasma PTH <300 pg/ml or a ≥30% decrease in PTH (secondary end points).

Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism.

Background And Objectives: Cinacalcet and vitamin D are often combined to treat secondary hyperparathyroidism (SHPT) in patients on dialysis. Independent effects on fibroblast growth factor-23 (FGF-23) concentrations in patients on hemodialysis administered cinacalcet or vitamin D analogs as monotherapies during treatment of SHPT are evaluated.

Design, Setting, Participants, & Measurements: A multicenter, randomized, open-label study to compare the efficacy of cinacalcet versus traditional vitamin D therapy for management of secondary hyperparathyroidism among subjects undergoing hemodialysis (PARADIGM) was a prospective, phase 4, multicenter, randomized, open-label study conducted globally.

A review of relative dose intensity and survival in patients with metastatic solid tumors.

Studies have shown that in the curative setting patients with cancer receiving chemotherapy at higher relative dose intensity (RDI) had better clinical outcomes than those receiving treatment at lower RDI. However, the impact of RDI in advanced/metastatic disease remains unclear. A review of the literature was performed to evaluate the relationship between RDI and survival in patients with metastatic lung, breast, or ovarian cancer receiving chemotherapy.

Presence of valvular calcification predicts the response to cinacalcet: data from the ADVANCE study.

Background And Aim Of The Study: Cardiac valve calcification (CVC) and coronary artery calcification (CAC) appear to be linked pathogenetically, and both are associated with a poor prognosis among patients with chronic kidney disease on dialysis (CKD-5D). Little is known, however, about factors that affect the progression of CVC and CAC.

Methods: A post-hoc analysis was performed of the ADVANCE study to assess whether patients with CVC are more prone to CAC progression, and whether CVC predicts the response to different treatments for secondary hyperparathyroidism.

Protocol adherence and the progression of cardiovascular calcification in the ADVANCE study.

Background: The ADVANCE study assessed the progression of vascular and cardiac valve calcification in 360 hemodialysis patients with secondary hyperparathyroidism (sHPT) assigned randomly to treatment either with cinacalcet plus low-dose vitamin D (≤ 6 µg/week of intravenous paricalcitol equivalent) or with varying doses of vitamin D alone for 52 weeks. The primary efficacy endpoint was progression of coronary artery calcification (CAC).

Methods: In this post-hoc analysis, we compared CAC progression among 70 protocol-adherent subjects given cinacalcet and low doses of vitamin D (CPA) as specified in the study protocol and 120 control subjects given vitamin D sterols.

Lack of correlation between epidermal growth factor receptor status and response to Panitumumab monotherapy in metastatic colorectal cancer.

Purpose: Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is approved as monotherapy for the treatment of metastatic colorectal cancer. We evaluated the association of tumor EGFR expression levels with outcomes in patients with chemorefractory metastatic colorectal cancer.

Experimental Design: Two phase II, multicenter, single-arm, open-label studies enrolled chemorefractory patients with tumors expressing low/negative (1-9%/<1%; Low/Negative EGFR study) or high (> or =10%; High EGFR study) levels of EGFR.

Association of K-ras mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab alone.

Background: Identifying predictive biomarkers is important to optimally treat patients. This analysis evaluated the association of K-ras, BRAF, and PIK3CA gene mutations with tumor resistance to panitumumab alone.

Patients And Methods: From 3 phase II panitumumab metastatic colorectal cancer (mCRC) studies, 62 of 533 patient samples were available.

Metaplastic breast cancer: clinical significance.

Background: Metaplastic breast carcinoma (MBC) is a rare poorly differentiated breast cancer characterized by coexistence of ductal carcinoma with areas of matrix producing, spindle-cell, sarcomatous, or squamous differentiation; ER/PR/HER2 negativity; and a reputation for poor outcome.

Methods: The Swedish Cancer Institute prospective breast cancer database (> 6500 patients; 1990-2005) has 24 MBC cases that were compared with typical breast cancer cases matched for age, date of diagnosis, stage, and ER/PR/HER2 status.

Results: The mean metaplastic primary tumor diameter was 2.