Treatment patterns and outcomes following disease progression on anti-PD-1 therapies for advanced melanoma.

Background: Anti-PD-1-based therapies prolong survival in advanced melanoma, but disease progression is common. This study evaluated treatment patterns and overall survival (OS) after anti-PD-1 progression. Methods: Retrospective data from patients with advanced melanoma and progression on anti-PD-1 treatment between 2014 and 2019 were taken from Flatiron Health, which reflects largely community practice. Treatment patterns and OS were analyzed for BRAF mutant (mt) and wild-type (wt) subgroups; OS was also examined across all patients. Results: Progression following anti-PD-1 was recorded for 679 patients. Median OS ranged from 5.0 to 11.3 months. Of 275 BRAFmt and 374 BRAFwt patients, 113 (41.1%) and 228 (61.0%) received no subsequent therapy, respectively. However, 48.4% of BRAFmt and 57.8% of BRAFwt patients continued anti-PD-1 treatment beyond progression. Conclusion: This real-world study underscores the need for effective treatments for advanced melanoma post-progression on anti-PD-1 therapy.

A multinational observational study assessing insulin use: Understanding the determinants associated with progression of therapy.

AIMS: To describe global patterns of insulin treatment and to assess the impact of patient, provider, health system and economic influences on treatment decisions for patients with insulin-treated type 2 diabetes (T2D). METHODS: This prospective cohort study of insulin-treated patients with T2D was conducted across 18 countries categorized as high, upper-middle or lower-middle income regions. Information collected from patients included knowledge of diabetes, experiences and interactions with their healthcare provider. Physician information included specialty, practice size, availability of diabetes support services, volume of diabetes patients treated and time spent per patient. Physicians determined an individualized haemoglobin A1c (HbA1c) target for each patient by the start of the study. Changes in T2D therapies and HbA1c were recorded for 2 years. RESULTS: Complete treatment data were available for 2528 patients. Median age was 61 years and median duration of diabetes was 11.4 years. Changes to treatment regimen occurred in 90.0% of patients, but changes were less common in countries with a higher economic status (P < 0.001). Most treatment changes involved insulin, with changes in dose the most common. Overall predictors of change in insulin therapy included younger age, use of any insulin regimen other than basal only, higher mean baseline HbA1c and longer duration of T2D. HbA1c levels remained constant regardless of regional economic status. At baseline, 20.6% of patients were at their HbA1c target; at 2 years this was 26.8%. CONCLUSIONS: Among insulin-treated patients with T2D, treatment changes were common; however, only approximately one-fourth of individuals achieved their HbA1c target.

Treatment patterns and overall survival in metastatic non-small-cell lung cancer in a real-world, US setting.

Aim: To conduct a retrospective analysis of electronic medical record data to understand real-world treatment patterns and overall survival (OS) in patients with metastatic non-small-cell lung cancer (NSCLC). Materials & methods: We included n = 9656 adults (≥18 years) with metastatic NSCLC and no prior therapy. Data from 1 January 2013 to 31 January 2017 were analyzed. Results: Carboplatin plus paclitaxel was the most common first-line therapy (18.6%), and nivolumab was the most common second- (31.0%) and third-line (38.4%) therapy; 26.7% of all patients were untreated. Median OS from initial metastatic diagnosis was 11.1 months (95% CI: 10.8-11.5). Second-line immunotherapy extended OS by over 3 months versus second-line chemotherapy. Conclusion: Platinum-based therapy was the most common first-line therapy, and immunotherapy was the most common second- and third-line therapy. Median OS of patients with metastatic NSCLC was <1 year.

Development and validation of algorithms to identify newly diagnosed type 1 and type 2 diabetes in pediatric population using electronic medical records and claims data.

PURPOSE: To develop and validate algorithms to classify diabetes type in newly diagnosed pediatric patients with DM. METHOD: Data from the United States Department of Defense health system were used to identify patients aged 10 to 18 years with incident DM. Two independent sets of 200 children were randomly sampled for algorithm development and validation. Algorithms were developed based on clinical insight, published literature, and quantitative approaches. The actual DM type was ascertained via chart review. Finally, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated. RESULTS: Among the 400 patients, mean age was 14.2 (±2.5 years), and 50% were female. The best performing algorithms were based on data available in claims. They consisted of several logical expressions based on one predictor or more, which classified patients by use of glucose-lowering drugs or testing, DM ICD-9 diagnosis codes, and comorbidities. The best performing T2DM and T1DM algorithms achieved 90% and 98% sensitivity, 95% and 95% specificity, 87% and 98% PPV, and 96% and 96% NPV, respectively. CONCLUSIONS: Our results suggest that claims algorithms can accurately identify newly diagnosed T1DM and T2DM pediatric patients, which can facilitate large database studies in children with T1DM and T2DM. However, external validation in other data sources is needed.

Real-world utilization of darbepoetin alfa in cancer chemotherapy patients.

OBJECTIVES: To provide an understanding of darbepoetin alfa dose patterns in cancer patients undergoing myelosuppressive chemotherapy starting from 2011. STUDY DESIGN: This is a retrospective cohort study using a proprietary outpatient oncology database. METHODS: Metastatic, solid tumor cancer patients receiving concomitant myelosuppressive chemotherapy and darbepoetin alfa with an associated hemoglobin <10 g/dL during 2011-2015 were identified. The analysis was restricted to the first continuous exposure to chemotherapy agents (maximum allowable gap of 90 days between consecutive exposures) with darbepoetin alfa for each eligible patient. Initial, maintenance, weekly, and cumulative doses of darbepoetin alfa were examined across all darbepoetin alfa users. Subgroup analyses were conducted by chemotherapy type, baseline hemoglobin level, year of chemotherapy, solid tumor type, and initial dosing schedule. Differences in weekly doses across subgroups were evaluated using Wilcoxon rank-sum tests. RESULTS: Among 835 eligible patients, over 90% were 50 years or older. Mean chemotherapy course duration was 248 days, and mean duration of darbepoetin alfa treatment was 106 days. The mean weekly darbepoetin alfa dose was 110 µg. Patients received a mean of 4.3 darbepoetin alfa injections in the first chemotherapy course. There were no statistically significant differences (all P values > .05) in weekly dose by chemotherapy type, baseline hemoglobin level, year of chemotherapy, or solid tumor type. CONCLUSION: The average weekly darbepoetin alfa dose among metastatic cancer patients with chemotherapy-induced anemia from this study was 110 µg, which was lower than the labeled dosage for most adults. This estimate did not differ over time, across chemotherapy regimens, baseline hemoglobin levels, or solid tumor types.

The risk of malignancy among biologic-naïve pediatric psoriasis patients: A retrospective cohort study in a US claims database.

BACKGROUND: Little published literature exists regarding malignancy risk in pediatric psoriasis patients. OBJECTIVE: To compare malignancy risk in biologic-naïve pediatric psoriasis patients with a matched pediatric population without psoriasis. METHODS: This retrospective cohort study used IMS LifeLink Health Plan Claims data covering 1998-2008. Cancer incidence was compared with the US Surveillance, Epidemiology, and End Results (SEER) data using standardized incidence ratios (SIR), and between cohorts using Cox models. RESULTS: Among 9045 pediatric psoriasis patients and 77,206 comparators, 18 probable or highly probable cancers were identified. Pediatric psoriasis patients had a nonsignificantly lower incidence than comparators (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.05-3.54). The HR increased to 1.67 (95% CI 0.54-5.18) when cancer diagnosed during the first 90 days of follow-up was included. The pediatric psoriasis cohort had a significantly increased lymphoma rate compared with SEER (SIR 5.42, 95% CI 1.62-12.94), but no significant increase relative to the comparator cohort. LIMITATIONS: Misclassification of disease and outcome might have occurred with patients in the claims database. CONCLUSION: Patients with pediatric psoriasis showed no significant increase in overall cancer risk compared with those without psoriasis. A potential increased risk for lymphoma was observed when compared with the general population.

Identification of metastatic cancer in claims data.

PURPOSE: To develop algorithms to identify metastatic cancer in claims data, using tumor stage from an oncology electronic medical record (EMR) data warehouse as the gold standard. METHODS: Data from an outpatient oncology EMR database were linked to medical and pharmacy claims data. Patients diagnosed with breast, lung, colorectal, or prostate cancer with a stage recorded in the EMR between 2004 and 2010 and with medical claims available were eligible for the study. Separate algorithms were developed for each tumor type using variables from the claims, including diagnoses, procedures, drugs, and oncologist visits. Candidate variables were reviewed by two oncologists. For each tumor type, the selected variables were entered into a classification and regression tree model to determine the algorithm with the best combination of positive predictive value (PPV), sensitivity, and specificity. RESULTS: A total of 1385 breast cancer, 1036 lung, 727 colorectal, and 267 prostate cancer patients qualified for the analysis. The algorithms varied by tumor type but typically included International Classification of Diseases-Ninth Revision codes for secondary neoplasms and use of chemotherapy and other agents typically given for metastatic disease. The final models had PPV ranging from 0.75 to 0.86, specificity 0.75-0.97, and sensitivity 0.60-0.81. CONCLUSIONS: While most of these algorithms for metastatic cancer had good specificity and acceptable PPV, a tradeoff with sensitivity prevented any model from having good predictive ability on all measures. Results suggest that accurate ascertainment of metastatic status may require access to medical records or other confirmatory data sources.

Risk of venous thromboembolism among women receiving ospemifene: a comparative observational study.

Introduction: The primary aim of this study was to compare the incidence of venous thromboembolism (VTE) among women initiating ospemifene vs other selective estrogen receptor modulator (SERM) therapies for estrogen-deficiency conditions or breast cancer prevention, and vs women with untreated vulvar and vaginal atrophy (VVA). The secondary objective examined numerous additional safety outcomes. Methods: This was a retrospective cohort study using the IBM Watson MarketScan claims database. Women receiving ospemifene, another SERM, or with a new diagnosis of VVA with no treatment from 1 May 2013 to 2 October 2018 were followed through the claims for incident adverse outcomes. The primary outcome was the first occurrence of VTE following cohort entry; secondary outcomes included cerebrovascular events and other adverse events potentially associated with SERM use. Cox models compared the risk of VTE between ospemifene and comparators, using a variety of approaches to control for confounding. Results: The incidence of VTE during the first continuous treatment episode was 3.39 (95% confidence interval [CI]: 1.55-6.43) events per 1,000 person-years (PY) for ospemifene (N = 8977), 11.30 (95% CI: 8.81-14.28) events per 1,000 PY for comparator SERM (N = 12,621), and 10.92 (95% CI: 10.49-11.37) events per 1,000 PY for untreated VVA (N = 242,488). Cox models indicated no increase in risk of VTE for ospemifene vs other SERMs (hazard ratio [HR]: 0.40, 95% CI: 0.19-0.82), and vs untreated VVA (HR: 0.47, 95% CI: 0.24-0.91). Conclusion: This real-world safety analysis found no increase in risk of VTE or other adverse events with use of ospemifene in postmenopausal women. Plain Language Summary: Introduction: This study assessed the risk of venous thromboembolism (VTE) among women treated with ospemifene or another selective estrogen receptor modulator (SERM) therapy and women with untreated vulvar and vaginal atrophy (VVA). Numerous additional safety outcomes were examined.Methods: This study was conducted in the IBM Watson MarketScan claims database. Women receiving ospemifene, another SERM, or with a new diagnosis of VVA with no treatment from 1 May 2013 to 2 October 2018 were followed through the claims for adverse outcomes, including VTE, cerebrovascular events (such as stroke), and other outcomes that might occur with use of a SERM. The analyses compared the risk of VTE between ospemifene and the other two groups, using methods that accounted for differences in patient characteristics between the groups. Because few women over 72 years old used ospemifene, the main analyses examined women aged 54-72 years.Results: The analyses included 8,977 ospemifene users, 12,621 other SERM users, and 242,488 women with untreated VVA. Among women aged 54-72 years, only 9 experienced a VTE during ospemifene treatment, while 55 other SERM users and 1,788 women with untreated VVA had a VTE. The analyses that accounted for differences between the groups confirmed that the risk of VTE was no higher in ospemifene users than in either comparison group.Conclusion: This real-world safety analysis found no increase in risk of VTE or other adverse events with use of ospemifene in postmenopausal women.

Individualized HbA1c target selection and achievement in the Multinational Observational Study Assessing Insulin Use (MOSA1c) type 2 diabetes study.

AIM: To identify which individual-, physician-, and the healthcare system-related factors can predict individualized hemoglobin A1c (HbA1c) targets and the likelihood of reaching those targets after initial insulin therapy over a two-year follow-up period. METHODS: Real-world data, including baseline characteristics of people with type 2 diabetes mellitus (T2DM), psychosocial data, and diabetes medication use, collected from the Multinational Observational Study Assessing Insulin Use (MOSA1c) study in 18 countries were analyzed. RESULTS: Overall, 225 of 1194 people with T2DM (18.8%) who received initial insulin therapy for ≥3 months reached HbA1c targets at two-year follow-up; most were likely to be White (64.9%) and perceptions of their relationship with physicians were less positive than those who did not reach HbA1c targets. Higher baseline HbA1c (>8%) was the strongest predictor of being assigned an HbA1c target >7% (odds ratio [OR] 6.06, 95% confidence interval [CI] 3.97, 9.26). A smaller difference between baseline and target HbA1c levels was the strongest predictor of reaching an HbA1c target at two-year follow-up (large vs small difference, OR 0.28, 95% CI 0.17, 0.47). CONCLUSIONS: Several factors were significantly associated with establishing individualized HbA1c targets and reaching these targets. A small proportion of people with T2DM on insulin therapy reached their HbA1c target. Personalized management of glycemic targets necessitates the adoption of multi-factorial strategies, as several factors could influence an individual's glycemic outcome. CLINICALTRIALS. GOV IDENTIFIER: NCT01400971.

A Real-World Evidence Study of CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status.

INTRODUCTION: Limited data exist on real-world treatment patterns and the effectiveness of cyclin-dependent kinase (CDK) 4/6 inhibitors in germline BRCA (gBRCA)-mutated breast cancer. METHODS: Adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) treated with CDK4/6 inhibitor therapy between 2013 and 2018 were retrospectively selected from the Flatiron Health database. Patients with known gBRCA status were classified as mutated (gBRCAm) or wild type (gBRCAwt). Time-to-first subsequent therapy or death (TFST) and overall survival (OS) were calculated from the earliest line of therapy with a CDK4/6 inhibitor. RESULTS: Of 2968 patients with HR+/HER2- mBC receiving a CDK4/6 inhibitor, 859 (28.9%) had known gBRCA status, of whom 9.9% were gBRCAm and 90.1% gBRCAwt. Median (95% confidence interval [CI]) TFST was 10 (7-11) months in the gBRCAm group, 10 (9-11) months in the gBRCAwt group, and 11 (10-12) months in the combined gBRCAwt and unknown gBRCA group; median (95% CI) OS was 26 (21-not estimated), 37 (31-51), and 33 (31-35) months, respectively. Cox models indicated the gBRCAm group had shorter TFST (stratified hazard ratio [sHR] 1.24; 95% CI 0.96-1.59) and OS (sHR 1.50; 95% CI 1.06-2.14) than the gBRCAwt group. The gBRCAm group had shorter TFST (sHR 1.38; 95% CI 1.08-1.75) and OS (sHR 1.22; 95% CI 0.88-1.71) than the combined group. CONCLUSION: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be worse in patients with gBRCAm mBC than in their counterparts with gBRCAwt and unknown gBRCA status, suggesting potential differences in tumor biology. This result highlights the unmet need in patients with gBRCAm requiring optimized treatment selection and sequencing. Future exploration in larger samples of patients who have had biomarker testing is warranted.

Incidence of venous thromboembolism among postmenopausal women prescribed ospemifene, selective estrogen receptor modulators for noncancer indications, or untreated vulvar and vaginal atrophy.

OBJECTIVE: Ospemifene is a nonsteroidal selective estrogen receptor modulator (SERM) for the treatment of moderate symptomatic vulvar and vaginal atrophy (VVA) due to menopause. A postauthorization safety study is currently examining the incidence of venous thromboembolism (VTE) among postmenopausal women receiving ospemifene or other SERM (raloxifene, bazedoxifene, or tamoxifen, for noncancer indications), or with untreated VVA. METHODS: This interim analysis used the US MarketScan Commercial and Medicare Supplemental claims database from 2013 to 2017 to identify incident VTE. The incidence rate and 95% confidence interval of VTE during the first continuous course of treatment (or continuous untreated time for the untreated cohort) were calculated for each cohort overall and by age group, with sensitivity analyses examining incidence in the short term (up to 90 days) and long term (all available follow-up, regardless of treatment changes). RESULTS: Analyses included 8,188 ospemifene users, 11,777 other SERM users, and 220,242 women with untreated VVA. The incidence per 1,000 person-years and 95% confidence interval of VTE were 3.7 (1.7-7.1) for ospemifene, 11.5 (8.9-14.6) for other SERM, and 11.3 (10.8-11.7) for untreated VVA. Stratification by age and altering the time frame for analysis produced results with similar patterns to the primary analysis. CONCLUSIONS: This interim analysis of an ongoing study suggests a favorable safety profile for ospemifene with respect to VTE. Comparative analyses with covariate adjustment will be performed when data accrual is complete.

Effectiveness of durvalumab versus chemotherapy in metastatic urothelial cancer: an observational, indirect comparison.

Aim: To compare the overall survival of patients with metastatic urothelial carcinoma (mUC) who failed platinum-based chemotherapy and received durvalumab or chemotherapy. Patients & methods: In an indirect comparison of patients with mUC who failed platinum-based chemotherapy, those who received durvalumab in a single-arm study were matched to patients from the Flatiron oncology electronic medical record database who received chemotherapy (n = 158 for each cohort). Matching was based on propensity scores. Kaplan-Meier methods and Cox regression models were utilized. Results: Median overall survival was 11.2 months (95% CI: 7.2-16.9) for durvalumab versus 8.2 months (95% CI: 6.7-9.8) for chemotherapy (hazard ratio: 0.63; 95% CI: 0.48-0.84). Conclusion: As a second-line therapy for mUC, durvalumab was associated with longer overall survival than chemotherapy.

STK11 (LKB1) mutations in metastatic NSCLC: Prognostic value in the real world.

BACKGROUND: Mutations in STK11 (STK11m) and frequently co-occurring KRAS mutations (KRASm/STK11m) are associated with poor survival in metastatic NSCLC (mNSCLC) immuno-oncology trials. There are limited data regarding the prognostic significance of these mutations in a real-world setting. METHODS: This retrospective cohort study analyzed de-identified electronic medical records from the Flatiron Clinico-Genomic database to identify patients with mNSCLC who had initiated first-line immunotherapy (IO; alone or in combination) or chemotherapy under routine care between January 1, 2013 and June 30, 2017. The primary objectives were to assess the prevalence of STK11m and KRASm/STK11m and to determine associations of these mutations with overall and progression-free survival (OS, PFS). RESULTS: Of 2407 patients with mNSCLC, STK11m and KRASm/STK11m were present in 13.6% and 6.5% of patients, respectively. Worse OS outcomes were observed in patients with STK11m versus STK11wt mNSCLC receiving IO (first-line, HR [95% CI], 1.4 [0.9-2.3; p = 0.1]; second-line [subset of first-line cohort], HR, 1.6 [1.3-2.0; p = 0.0002]) or chemotherapy (first-line, HR, 1.4 [1.2-1.6; p < 0.0001]); PFS outcomes showed similar trends. KRASm/STK11m double mutations were associated with worse OS and PFS outcomes versus KRASwt/STK11wt with IO and chemotherapy, similar to the single mutation (STK11m vs STK11wt) findings. CONCLUSIONS: This large observational genomic study among patients receiving routine care highlights the negative prognostic impact of STK11m in patients with mNSCLC treated with IO or chemotherapy. These results complement previous clinical trial data and provide further evidence in the real world of a patient population that would benefit from new treatment options.

Commonly used definitions in real-world studies may underestimate the prevalence of renal disease among nonvalvular atrial fibrillation patients.

Aim: To describe comorbidities among treated nonvalvular atrial fibrillation (NVAF) patients and assess the impact of using different time ('look back' windows) on the prevalence estimates. Patients & methods: We included all adult nonvalvular atrial fibrillation patients newly initiating treatment in the Clinical Practice Research Datalink. Comorbidities included in the Charlson Comorbidity Index were defined using an all available, 3- and 1-year look back window before the start of treatment. Results: The prevalence of comorbidities was high and increased when using longer look back windows; the largest difference was observed for renal disease (+15.6%). Conclusion: Our findings emphasize the importance of using all available data when characterizing chronic conditions and highlights the high comorbidity burden in this population.

Treatment patterns and overall survival in metastatic urothelial carcinoma in a real-world, US setting.

BACKGROUND: Metastatic urothelial carcinoma (mUC) treated with chemotherapy is associated with poor survival; however, as the field of immuno-oncology continues to evolve, new immunotherapies have recently become available. The current study aimed to assess real-world characteristics, treatment patterns, and overall survival (OS) of patients with mUC treated in the United States (US). METHODS: We conducted a retrospective, observational analysis of patients with mUC from the Flatiron Health longitudinal database from 2011 to 2017. Treatment patterns of patients who started systemic first-line therapy (1 L cohort) or second-line therapy following platinum-based first-line therapy (2 L cohort) were described using medication order and administration data. Kaplan-Meier analyses were used to assess OS from the start of first- and second-line therapy in the 1 L and 2 L cohorts, respectively. RESULTS: A total of 1811 patients qualified for the 1 L cohort (median age [range], 72 [32-84] years); 476 met the criteria for the 2 L cohort (median age [range], 71 [40-84] years). The most common first- and second-line therapies were carboplatin + gemcitabine (n = 562 [34.6%]) and atezolizumab (n = 90 [13.1%]), respectively, in the 1 L cohort. Median OS was 12.7 months (95% confidence interval [CI] 11.8, 13.4) in the 1 L cohort and 8.3 months (95% CI 7.2, 8.9) in the 2 L cohort. CONCLUSIONS: Consistent with clinical trial results, survival was poor in this real-world study in patients with mUC, indicating a continued unmet need. As immunotherapy becomes more commonplace in the treatment of mUC, future studies are needed to understand its real-world impact on survival.

Prescriber Compliance With Liver Monitoring Guidelines for Pazopanib in the Postapproval Setting: Results From a Distributed Research Network.

OBJECTIVES: Pazopanib received US Food and Drug Administration approval in 2009 for advanced renal cell carcinoma. During clinical development, liver chemistry abnormalities and adverse hepatic events were observed, leading to a boxed warning for hepatotoxicity and detailed label prescriber guidelines for liver monitoring. As part of postapproval regulatory commitments, a cohort study was conducted to assess prescriber compliance with liver monitoring guidelines. METHODS: Over a 4-year period, a distributed network approach was used across 3 databases: US Veterans Affairs Healthcare System, a US outpatient oncology community practice database, and the Dutch PHARMO Database Network. Measures of prescriber compliance were designed using the original pazopanib label guidelines for liver monitoring. RESULTS: Results from the VA (n = 288) and oncology databases (n = 283) indicate that prescriber liver chemistry monitoring was less than 100%: 73% to 74% compliance with baseline testing and 37% to 39% compliance with testing every 4 weeks. Compliance was highest near drug initiation and decreased over time. Among patients who should have had weekly testing, the compliance was 56% in both databases. The more serious elevations examined, including combinations of liver enzyme elevations meeting the laboratory definition of Hy's law were infrequent but always led to appropriate discontinuation of pazopanib. Only 4 patients were identified for analysis in the Dutch database; none had recorded baseline testing. CONCLUSIONS: In this population-based study, prescriber compliance was reasonable near pazopanib initiation but low during subsequent weeks of treatment. This study provides information from real-world community practice settings and offers feedback to regulators on the effectiveness of label monitoring guidelines.

Discontinuation and primary care visits in nonvalvular atrial fibrillation patients treated with apixaban or warfarin.

AIM: Nonvalvular atrial fibrillation (NVAF) requires long-term anticoagulation treatment, which may necessitate frequent primary care visits. MATERIALS & METHODS: NVAF patients initiating warfarin or apixaban in 2012-2017 were identified from linked primary (Clinical Practice Research Datalink) and secondary care (Hospital Episode Statistics) data. A propensity score matched Cox regression model compared discontinuation risk. Primary care visits were compared via negative binomial regression. RESULTS: A total of 2695 apixaban users were matched to warfarin patients. Discontinuation risk was lower with apixaban than warfarin (hazard ratio: 0.40; 95% CI: 0.35-0.46). Apixaban patients averaged 12.2 annual primary care visits, versus 17.1 for warfarin users (p < 0.001). CONCLUSION: Apixaban was associated with reduced rates of discontinuation and primary care visits compared with warfarin.

Adherence to guidelines for use of erythropoiesis-stimulating agents in patients with chemotherapy-induced anemia: results of a retrospective study of an electronic medical-records database in the United States, 2002-2006.

BACKGROUND: Chemotherapy-induced anemia (CIA) commonly occurs in cancer patients receiving conventional myelosuppressive chemotherapy. Two national guidelines regarding the use of erythropoiesis-stimulating agents (ESAs) in CIA were released in 2002. Because of poorer disease outcomes and increased risk of adverse events associated with ESAs in recent studies, the use of ESAs has been increasingly restricted in practice guidelines in the years 2007 and 2008. OBJECTIVE: The aim of this study was to provide a baseline for adherence to national guidelines in the use of ESAs for CIA between 2002 and 2006. METHODS: This retrospective study used the Varian Medical Oncology database (Varian Medical Systems, Inc., Palo Alto, California) of electronic medical records, representing 17 outpatient oncology organizations at 71 clinic locations in the United States. Adults diagnosed with any malignant neoplasm who started conventional cytotoxic chemotherapy between January 1, 2002, and September 30, 2006, were included. The proportion of patients receiving an ESA was calculated by hemoglobin (Hb) level during each chemotherapy cycle, stratified by line of chemotherapy and year. Logistic regression modeling identified predictors of ESA use in anemic patients during the first chemotherapy cycle. RESULTS: The records of 17,731 cancer patients were evaluated. Median (SD) age was 61 (13) years, and 58.9% were female. Most patients (84.1%) had a solid tumor. Many patients (41.3%) received platinum containing chemotherapy and 74.4% received combination chemotherapy. During the first 5 cycles of first-line chemotherapy among patients with CIA (Hb <11 g/dL), ESAs were used by 55.8% of patients at cycle 1 and 68.9% at cycle 5. ESA use in CIA patients increased across lines of chemotherapy and time. Few patients (2.8%) received an ESA at Hb >13 g/dL. The statistically significant predictors of ESA use included age >65 years, eastern US residence, private health insurance, community-based care, and solid tumors, especially lung cancer. CONCLUSION: The patterns we observed were generally consistent with prevailing ESA labels and national guidelines during 2002 through 2006. Although ESA use in patients with CIA increased over chemotherapy cycles, lines of chemotherapy, and time, <70% of CIA episodes were treated with ESAs during the initial 5 chemotherapy cycles.

Use of erythropoiesis-stimulating agents among chemotherapy patients with hemoglobin exceeding 12 grams per deciliter.

BACKGROUND: Prior to 2007, the erythropoiesis-stimulating agents (ESAs) epoetin alfa and darbepoetin alfa were indicated for use in chemotherapyinduced anemia to achieve target hemoglobin (Hb) levels of approximately 12 grams per deciliter (gm per dL), and treatment was to be withheld if Hb exceeded 13 gm per dL. In March 2007, the FDA changed the labeling of the ESAs to add boxed warnings, updated in November 2007, to include the following key points: (a) ESAs should be used only to treat anemia that occurs in patients with cancer while they are undergoing chemotherapy; (b) treatment with ESAs should be stopped when chemotherapy ends; and (c) dosing ESAs to an Hb target of 12 gm per dL or greater has resulted in more rapid cancer progression or shortened overall survival in patients with breast, head and neck, lymphoid, cervical, and non-small cell lung malignancies. In January 2008, the FDA specified that the increased risk of more rapid tumor growth or shortened survival was associated with ESAs when "administered in an attempt to achieve a Hb level of 12 gm per dL or greater, although many patients did not reach that level." A new black-box warning regarding this association was added to the labels of the ESAs in March 2008, and the FDA mandated further label changes on July 30, 2008, that ESA therapy should not be initiated in patients receiving chemotherapy at Hb levels of 10 gm per dL or higher. OBJECTIVE: To (a) assess the prevalence and predictors of ESA administrations at Hb levels above 12 gm per dL among patients with a diagnosis of solid or hematologic cancer or myelodysplastic syndrome who began their first regimen of conventional myelosuppressive chemotherapy between 2002 and 2006, and (b) describe patterns of ESA treatment subsequent to the first ESA administration at Hb above 12 gm per dL. METHODS: Using the Health Insurance Portability and Accountability Act (HIPAA)-compliant Varian Medical Oncology database of de-identified electronic medical records from 17 U.S. outpatient oncology practices, adults (aged 18 years or older) with any cancer diagnosis who began chemotherapy between January 1, 2002, and September 30, 2006, were identified. The Hb value associated with each ESA administration was defined as the closest Hb measurement within 7 days prior to the ESA administration. A first ESAHb > 12 was defined as the first time an ESA, either epoetin or darbepoetin, was given with an associated Hb greater than 12 gm per dL during the first chemotherapy regimen recorded in the database for each patient. Hb levels and ESA administrations after the first ESAHb > 12 were determined. Logistic regression models identified predictors of initial receipt of an ESAHb > 12, and of receiving further ESA treatment following the first such administration. RESULTS: Between January 1, 2002, and September 30, 2006, there were 17,731 patients on chemotherapy, the mean (SD) age was 60 (13.2) years; 58.9% were female; 24.6% had breast cancer, 22.2% had lung cancer, 15.8% had colorectal cancer, 11.8% had hematologic cancer, and 25.6% had other or multiple cancers. Of these, 8,086 (45.6%) received an ESA at any time during the regimen, and 7,606 (42.9%) received an ESA at a known Hb level (i.e., Hb measurement within 7 days prior to ESA administration). During the first recorded chemotherapy regimen, 1,844 patients (10.4% of the chemotherapy cohort, 24.2% of ESA users with a known Hb; n = 1,226 epoetin, n = 618 darbepoetin) received an ESAHb > 12. Among patients receiving ESA treatment at a known Hb level, significant predictors of receiving an ESAHb > 12 included treatment in a community-based clinic rather than a hospital-affiliated clinic (odds ratio [OR] = 2.96, 95% confidence interval [CI] = 2.40-3.65), location of practice in the eastern United States (OR for Midwest = 0.67, 95% CI = 0.57- 0.78; OR for West = 0.27, 95% CI = 0.22-0.34), hematologic cancer rather than solid tumor (OR = 1.44, 95% CI = 1.21-1.71), private health insurance (OR for public health insurance = 0.80, 95% CI = 0.70-0.93; OR for other/ unknown insurance = 0.54, 95% CI = 0.47-0.62), and year of regimen 2002- 2003 (ORs = 0.75, 0.74, and 0.71 for 2004, 2005, and 2006, respectively). Following the first ESAHb > 12, 276 (22.5%) of the patients on epoetin and 276 (44.7%) on darbepoetin received no further ESA treatment during the next 6 weeks (Pearson chi-square = 96.1, P < 0.001). CONCLUSIONS: This analysis of outpatient oncology practices between 2002 and 2006 revealed that 24% of ESA users with a known Hb level received ESAHb > 12. Dose withholding subsequently occurred in 23%- 45% of those patients. A higher proportion of patients on epoetin than darbepoetin continued ESA treatment after the first administration of ESAHb > 12.

Replication of Mini-Sentinel Study Assessing Mirabegron and Cardiovascular Risk in Non-Mini-Sentinel Databases.

BACKGROUND: In 2014, the US Food and Drug Administration (FDA) initiated a prospective routine surveillance using the Mini-Sentinel (M-S) program to assess potential signals of acute myocardial infarction (AMI) and stroke with use of mirabegron, indicated for the treatment of overactive bladder (OAB), compared with oxybutynin. PURPOSE: To replicate the FDA M-S analysis of mirabegron using datasets that did not contribute to the M-S program. METHODS: IMS PharMetrics Plus and Truven MarketScan claims data from 2012-2015 were converted to the M-S Common Data Model. New and non-new users of mirabegron and oxybutynin were analyzed per the publicly available M-S protocol, and propensity score-matched 1:1 using the M-S PROMPT 2 module. Incidence rates (IR) were calculated per 1000 person-years (PY). Adjusted hazard ratios (aHRs) for mirabegron versus oxybutynin were calculated using Cox regression models. RESULTS: In PharMetrics, 12,429 new mirabegron users and 61,548 new oxybutynin users were identified. The aHR was 0.67 (95% confidence interval (CI)] 0.33-1.37) for AMI (mirabegron IR 4.4/1000 PY), and 0.62 (95% CI 0.34-1.13) for stroke (mirabegron IR 6.3/1000 PY). In MarketScan, 17,182 new mirabegron users and 63,962 new oxybutynin users were identified. The aHR was 0.57 (95% CI 0.17-1.95) for AMI, and 0.69 (95% CI 0.30-1.62) for stroke; IRs were similar to those from PharMetrics. Neither dataset suggested an increased risk of AMI or stroke associated with mirabegron in non-new users. CONCLUSIONS: Using the publicly-available M-S protocol and analysis programs with alternative (non M-S) data sources, no statistically significant increased risk of AMI or stroke was found among new or non-new users of mirabegron compared with oxybutynin. These findings were consistent with the FDA M-S mirabegron study.