Real-world treatment patterns, healthcare resource utilization, and cost among adults with pulmonary arterial hypertension in the United States.

Treatment for pulmonary arterial hypertension (PAH) has evolved over the past decade, including approval of new medications and growing evidence to support earlier use of combination therapy. Despite these changes, few studies have assessed real-world treatment patterns, healthcare resource utilization (HCRU), and costs among people with PAH using recent data. We conducted a retrospective cohort study using administrative claims from the HealthCore Integrated Research Database®. Adult members with claims for a PAH diagnosis, right heart catheterization, and who initiated PAH treatment (index date) between October 1, 2015 and November 30, 2020 were identified. Members had to be continuously enrolled in the health plan for 6 months before the index date (baseline) and ≥30 days after. Treatment patterns, HCRU, and costs were described. A total of 843 members with PAH (mean age 62.3 years, 64.2% female) were included. Only 21.0% of members received combination therapy as their first-line treatment, while most members (54.6%) received combination therapy as second-line treatment. All-cause HCRU remained high after treatment initiation with 58.0% of members having ≥1 hospitalization and 41.3% with ≥1 emergency room visit. Total all-cause costs declined from $15,117 per patient per month at baseline to $14,201 after treatment initiation, with decreased medical costs ($14,208 vs. $6,349) more than offsetting increased pharmacy costs ($909 vs. $7,852). In summary, despite growing evidence supporting combination therapy, most members with PAH initiated treatment with monotherapy. Total costs decreased following treatment, driven by a reduction in medical costs even with increases in pharmacy costs.

How Assessment-Schedule Matching Limits Bias When Comparing Progression-Free Survival in Single-Arm Studies: An Application in Second-Line Urothelial Carcinoma Treatments.

OBJECTIVES: Population-adjusted comparisons of progression-free survival (PFS) from single-arm trials of cancer treatments can be derived using matching-adjusted indirect comparisons (MAICs); however, results are still susceptible to bias, particularly if the trials had different tumor assessment schedules. This study aims to assess the effects of assessment-schedule matching (ASM) on the relative effectiveness on the PFS of avelumab versus approved comparator immunotherapies or chemotherapy after population matching in the second-line (2L) setting for metastatic urothelial carcinoma. METHODS: The MAIC used patient-level data for avelumab from the JAVELIN Solid Tumor trial (NCT01772004). PFS was compared with published curves for other treatments to obtain population-adjusted hazard ratios (HRs). The MAIC was repeated after conducting ASM for differences in tumor assessment scheduled first at 6 weeks for avelumab and durvalumab and at 8 or 9 weeks for other treatments. RESULTS: MAIC adjustment alone altered the HR estimates up to 23%, whereas MAIC plus ASM resulted in up to 32.7% reductions from naive comparisons. Even in cases in which MAIC had little effect, ASM brought an additional change of 11.1% to 15.4%. Overall, the HR range of avelumab versus other treatments changed from 0.83 to 1.25 for naive comparisons to 0.76 to 0.99 after ASM plus MAIC, numerically favoring avelumab. CONCLUSIONS: Small variations in assessment schedules can introduce bias in unanchored indirect treatment comparisons of interval-censored time-to-event outcomes. In this study, adjusted PFS was comparable across second-line urothelial carcinoma treatment options, numerically favoring avelumab versus immunotherapies and chemotherapy agents. Correcting this bias is especially important when HRs are applied in cost-effectiveness models to transition patients between states.

Real-World Clinical and Economic Outcomes in Selected Immune-Related Adverse Events Among Patients with Cancer Receiving Immune Checkpoint Inhibitors.

BACKGROUND: With increased use of immune checkpoint inhibitors (ICIs) among patients with cancer, there is substantial interest in understanding clinical and economic outcomes and management of immune-related adverse events (irAEs). PATIENTS, MATERIALS, AND METHODS: A retrospective study was conducted using Premier Healthcare Database, a U.S. national hospital discharge database, from March 1, 2015, through December 31, 2017. The database comprises more than 880 million inpatient and hospital-based outpatient encounters, with more than 200 million unique patients reported by 966 hospitals. Patients with four solid tumors known to benefit from ICI therapy were included. The list of irAEs assessed was defined a priori per American Society of Clinical Oncology clinical guidelines for irAE management. Baseline irAE-related inpatient and outpatient visits were defined as the first inpatient or hospital-based outpatient visit with discharge diagnosis of any irAE of interest following confirmed ICI usage within 90 days prior to the baseline visit. Patients were followed for 90 days after baseline irAE-related inpatient discharge date or outpatient visit date to assess irAE-related inpatient admissions, all-cause in-hospital mortality, ICI reinitiation, and to determine costs and health care resource utilization. RESULTS: Records from 673,957 patients with four tumor types were reviewed for ICI therapy. Of 13,030 patients receiving ICIs, approximately 40% experienced at least one irAE, with a total of 10,121 irAEs occurring within 90 days of the ICI visit. The most frequent (>1,000 events) irAEs were anemia, impaired ventricular function with heart failure and vasculitis, thrombocytopenia, thyroid conditions, and peripheral edema. As might be expected, compared with those with baseline irAE-related outpatient visits, patients with baseline irAE-related inpatient visits had a significantly higher percentage of irAE-related inpatient admissions (23% vs. 14%) and all-cause in-hospital mortality (22% vs. 6%) and lower reinitiation of ICI therapy (31% vs. 71%). Baseline irAE-related inpatient visits had significantly higher mean costs ($29,477 vs. $5,718) with longer hospital stays (12.6 vs. 7.8 days). CONCLUSION: Findings from a U.S. national hospital discharge database suggest that irAEs in patients treated with ICIs are common, occur in multiples and with greater frequency in those with pre-existing comorbidities. Those with inpatient admissions have poorer outcomes. IMPLICATIONS FOR PRACTICE: The present work addressed the knowledge gap in understanding real-world outcomes of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs). Patients who experienced irAEs had significantly higher baseline comorbidities and were more likely to have immune-related or immune-compromised comorbid conditions. Patients with baseline irAE-related hospitalizations were more likely to be rehospitalized and to experience in-hospital mortality and less likely to reinitiate ICI treatment. Real-world patients are more diverse than clinical trials, and clinicians should consider both the efficacy and safety profile of ICI treatments, especially for patients with comorbidity conditions. Close monitoring is needed after patients have experienced an irAE.

Clinical Outcomes, Costs, and Healthcare Resource Utilization in Patients with Metastatic Merkel Cell Carcinoma Treated with Immune Checkpoint Inhibitors vs Chemotherapy.

PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with poor prognosis. This study compared patient characteristics, comorbidities, adverse events (AEs), treatment persistence, healthcare resource utilization (HRU) and costs in patients with metastatic MCC (mMCC) treated with immune checkpoint inhibitors (ICIs) or recommended chemotherapy per 2018 National Comprehensive Cancer Network (NCCN) Guidelines. PATIENTS AND METHODS: A retrospective, observational study was conducted using data from 3/1/2015 through 12/31/2017 from the Premier Healthcare Database, a US hospital discharge database. The study included patients aged ≥12 years with International Classification of Diseases Codes for MCC and metastasis, categorized by their first treatment (index) during the study period (ICI or NCCN-recommended chemotherapy [chemotherapy]). Patient, hospital, and visit characteristics were assessed at the index date and Charlson Comorbidity Index (CCI) score and comorbidities during a 6-month look-back period. Clinical outcomes, including AEs and treatment persistence were assessed over 90 days and HRU and costs over 180 days post-index. RESULTS: Of 75 patients with mMCC receiving ICIs (n=37) or chemotherapy (n=38), mean age was ≈73 years, and 21.3% had a history of immune-related (IR) conditions. Overall, ICI- and chemotherapy-treated patients were similar in most baseline characteristics, IR comorbidities, and CCI score. However, more ICI patients (46%) than chemotherapy patients (26%) persisted on treatment over 90-day follow-up, odds ratio (95% CI): 2.04 (0.93, 4.47), P=0.07. Over 180-day follow-up, 33% of patients had an inpatient admission with mean length of stay (LOS) ≈2 days shorter for ICI vs chemotherapy (not statistically significant). Total costs, primarily driven by pharmacy costs, were higher for ICIs than chemotherapy; other departmental costs were similar between treatment groups. CONCLUSION: In a real-world setting, patients with mMCC receiving ICIs had higher treatment persistence over 90 days, shorter inpatient LOS and similar departmental cost (excluding pharmacy cost) than those receiving chemotherapy.

Real-World Outcomes Among US Veterans Health Administration Patients Newly Diagnosed with Metastatic Renal Cell Carcinoma and Treated with First-Line Monotherapy.

INTRODUCTION: Substantial unmet needs exist among patients with metastatic renal cell carcinoma (mRCC). This retrospective study evaluated treatment patterns as well as clinical and economic outcomes associated with first-line monotherapy among patients with mRCC in the USA. METHODS: Newly diagnosed patients with mRCC initiating at least one first-line therapy (1L) from 1 October 2013 to 31 March 2018 (index date = 1L start date) were identified from the US Veterans Health Administration database. Treatment patterns, clinical outcomes (time to next treatment [TNT] defined by earliest of switch to non-index therapy or re-initiation of index therapy after a more than 90-day gap, time to treatment discontinuation [TTD], overall survival [OS]), and costs were evaluated among patients treated with tyrosine kinase inhibitors (TKI), mammalian target of rapamycin inhibitors (mTOR), immune checkpoint inhibitors (ICI), and other monotherapies. Standard descriptive statistics were presented. The Kaplan-Meier method was used to evaluate clinical outcomes. RESULTS: Of 759 patients (median age 68.0 years), 85.0%, 8.0%, 4.3%, and 2.6% were treated with TKI, mTOR, ICI, or other therapy in 1L, respectively. Advancement rates (to second-line [2L] therapy) ranged from 10.0 (ICI) to 45.1 per 100 person years (TKI). The 12-month OS rates ranged from 47.4% (TKI) to 67.7% (mTOR). The median TNT ranged from 3.8 (mTOR) to 9.6 months (ICI), and median TTD ranged from 2.3 (mTOR) to 4.7 months (TKI). Total all-cause mean costs per patient per month ranged from $12,466 (mTOR) to $19,812 (ICI). CONCLUSION: These results indicate high unmet medical needs among patients with mRCC treated with 1L monotherapies. Novel combination therapies (e.g., ICI + ICI, ICI + TKI) may improve front-line outcomes for patients with poor prognoses.

Treatment Sequencing Patterns in Patients with Metastatic Urothelial Cancer Treated in the Community Practice Setting in the United States: SPEAR-Bladder (Study informing treatment Pathway dEcision in bladder cAnceR).

PURPOSE: Clinical trial evidence has affirmed the role for immuno-oncology (IO) treatment for locally advanced or metastatic urothelial carcinoma (la/mUC). This Study informing treatment Pathway dEcision in bladder cAnceR (SPEAR-Bladder) aimed to provide insight into the optimal sequencing of IO treatments among la/mUC patients treated in the US Oncology Network. PATIENTS AND METHODS: This was a retrospective analysis of adult patients with la/mUC who initiated first-line chemotherapy followed by either IO therapy (C-IO subgroup) or chemotherapy (C-C subgroup) between 01/01/2015 and 04/30/2017 and included a potential follow-up period through 06/30/2017. Data were sourced from iKnowMed electronic health records. Patient and treatment characteristics were assessed descriptively, with Kaplan-Meier methods used to evaluate time-to-event outcomes, including overall survival (OS). RESULTS: A total of 117 patients were included in this analysis (median age 69 years, 74.4% male, 88.0% Caucasian): 79 and 38 patients were in the C-IO and C-C subgroups, respectively. The median OS was 19.2 months among patients who received the C-IO sequence and 11.9 months among those who received the C-C treatment sequence. CONCLUSION: These results suggest that patients who received the C-IO treatment sequence had notable improvement in OS compared with those who received the C-C sequence. In light of the rapidly evolving therapeutic landscape, further investigation will be required to determine how best to select the optimal therapeutic regimen and sequencing for patients with la/mUC.

Real-world outcomes among US Merkel cell carcinoma patients initiating immune checkpoint inhibitors or chemotherapy.

Aim: Retrospectively assessed treatment patterns and clinical and economic outcomes in Merkel cell carcinoma (MCC) patients receiving recommended first-line regimens. Materials & methods: MCC patients newly treated with either immune checkpoint inhibitors (ICIs) or chemotherapies (CTs) were selected from the Veterans Health Administration database (2013-2018); 74 patients (ICIs: 20 and CTs: 54) were selected. Results: Median duration of therapy was 300 days for ICIs and 91 days for CTs. Time to next treatment was 245 and 184 days, respectively. Mean total (per patient per month) costs were $15,306 (ICIs) and $10,957 (CTs), of which 51% and 86%, respectively, were non-MCC therapy-related costs. Conclusion: Despite higher costs, utilization of ICIs in first-line MCC shows clinical advantages over CTs in the real world.

Budget Impact Of Including Avelumab As A Second-Line Treatment For Locally Advanced Or Metastatic Urothelial Cancer In The United States: Commercial And Medicare Payer Perspectives.

OBJECTIVE: To estimate the budget impact of introducing avelumab as a second-line (2L) treatment option for patients with locally advanced or metastatic urothelial cancer (mUC) from the perspective of a US third-party payer (commercial and Medicare). METHODS: A budget impact model (BIM) with a three-year time horizon was developed for avelumab. Efficacy and safety data were sourced from published literature and US package inserts. The analysis was conducted in collaboration with a specialist oncologist who validated clinical assumptions. Costs were based on the number of eligible patients, time-to-treatment failure, overall survival, adverse events (AEs), and projected market shares of various treatments. RESULTS: In a hypothetical commercial health plan of 30,000,000 members, 884 patients were estimated to be eligible for 2L treatment over a three-year time period. Without avelumab, the total cost for treating patients with mUC was estimated to be US$70,268,035. The introduction of avelumab increased total costs by $73,438 (0.10% increase). In a hypothetical Medicare health plan of 30,000,000 beneficiaries, a total of 4,705 patients were estimated to be eligible for 2L treatment. Without avelumab, the total cost for treating patients with mUC was estimated to be $292,923,098 from a Medicare perspective; however, with avelumab, there was an increase of $719,324 (0.25% increase) in total costs. Results of the sensitivity analyses demonstrated a cost-neutral impact across all tested scenarios from both perspectives. CONCLUSION: The BIM estimated that avelumab would have a cost-neutral impact within a US commercial and a Medicare health plan. Overall, avelumab can be an affordable and valuable treatment option for patients with locally advanced or mUC in the 2L setting. These findings demonstrate a consistently favorable budget impact in both populations. Further studies should be conducted to more comprehensively assess the clinical and economic implications of adding avelumab to the treatment armamentarium of 2L mUC.

Value assessment of immuno-oncology in the treatment of rare tumors in the era of accelerated conditional approvals.

Aim: To conduct a value assessment of an immuno-oncology (IO) therapy for a rare cancer and evaluate whether existing frameworks consider challenges associated with valuing IOs for rare cancers. Materials & methods: Value frameworks developed by American Society of Clinical Oncologists, Memorial Sloan Kettering Cancer Center and National Comprehensive Cancer Network were used to estimate the value of an IO therapy in a rare cancer based on single-arm trial data and retrospective studies. Results: Paucity of direct evidence comparing rare cancer treatments and lack of acceptance of indirect comparisons hinder appropriate value assessment. Measurement of value based on short-term outcomes may not capture the value of IOs, where survival is often characterized by a plateau. Conclusion: Further work is required to factor in nuances associated with rare cancers and guide end users of the frameworks. To capture true value, multiple or more holistic value assessments are required.

Assessment-Schedule Matching in Unanchored Indirect Treatment Comparisons of Progression-Free Survival in Cancer Studies.

BACKGROUND: The timing of efficacy-related clinical events recorded at scheduled study visits in clinical trials are interval censored, with the interval duration pre-determined by the study protocol. Events may happen any time during that interval but can only be detected during a planned or unplanned visit. Disease progression in oncology is a notable example where the time to an event is affected by the schedule of visits within a study. This can become a source of bias when studies with varying assessment schedules are used in unanchored comparisons using methods such as matching-adjusted indirect comparisons. OBJECTIVE: We illustrate assessment-time bias (ATB) in a simulation study based on data from a recent study in second-line treatment for locally advanced or metastatic urothelial carcinoma, and present a method to adjust for differences in assessment schedule when comparing progression-free survival (PFS) against a competing treatment. METHODS: A multi-state model for death and progression was used to generate simulated death and progression times, from which PFS times were derived. PFS data were also generated for a hypothetical comparator treatment by applying a constant hazard ratio (HR) to the baseline treatment. Simulated PFS times for the two treatments were then aligned to different assessment schedules so that progression events were only observed at set visit times, and the data were analysed to assess the bias and standard error of estimates of HRs between two treatments with and without assessment-schedule matching (ASM). RESULTS: ATB is highly affected by the rate of the event at the first assessment time; in our examples, the bias ranged from 3 to 11% as the event rate increased. The proposed method relies on individual-level data from a study and attempts to adjust the timing of progression events to the comparator's schedule by shifting them forward or backward without altering the patients' actual follow-up time. The method removed the bias almost completely in all scenarios without affecting the precision of estimates of comparative effectiveness. CONCLUSIONS: Considering the increasing use of unanchored comparative analyses for novel cancer treatments based on single-arm studies, the proposed method offers a relatively simple means of improving the accuracy of relative benefits of treatments on progression times.

Survival Analysis in Patients with Metastatic Merkel Cell Carcinoma Treated with Avelumab.

INTRODUCTION: Complex underlying risk functions associated with immuno-oncology treatments have led to exploration of different methods (parametric survival, spline, landmark, and cure-fraction models) to estimate long-term survival outcomes. The objective of this study was to examine differences in estimated short- and long-term survival in previously treated metastatic Merkel cell carcinoma (mMCC) patients receiving avelumab, when using alternative extrapolation approaches. METHODS: Efficacy data from the phase 2 JAVELIN Merkel 200 trial (part A) with at least 12 months of follow-up were analyzed. Standard parametric survival analyses and analyses of overall survival (OS) as a function of surrogate outcomes comprised of response (landmark analyses) and progression-free survival plus post-progression survival (PFS + PPS) were used to project OS. Overall survival throughout lifetime was projected and compared with the observed OS data with at least 24 months of follow-up. RESULTS: Estimated OS from all three approaches provided a good fit to the observed OS curve from at least 12 months of follow-up. However, performance compared with OS data from at least 24 months showed that the landmark approach followed by PFS + PPS provided a better fit to the data as compared to standard parametric analysis. Mean life expectancy estimated with avelumab was 2.48 years with best-fitting parametric function (a log-normal distribution), 3.15 years with the landmark approach, and 3.54 years with PFS + PPS. CONCLUSION: Although standard parametric survival analysis may provide a good fit to short-term survival, it appears to underestimate the long-term survival benefits associated with avelumab in mMCC. Extrapolations based on surrogate outcomes of response or progression predict OS outcomes from longer follow-up better and appear to provide more clinically plausible projections. FUNDING: EMD Serono Inc, Rockland, MA, a business of Merck KGaA, Darmstadt, Germany.

Treatment Patterns, Overall Survival, and Total Healthcare Costs of Advanced Merkel Cell Carcinoma in the USA.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive type of cancer with poor outcomes. OBJECTIVE: To describe treatment patterns, overall survival, and healthcare costs associated with advanced MCC (aMCC) using data from Medicare enrollees who received an aMCC diagnosis in the USA States between 2006 and 2013. METHODS: Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2006 to 2013 were used to describe treatment patterns, 1- and 5-year overall survival, and total healthcare costs for the periods 12 months before aMCC diagnosis and 4-12 months afterward in patients aged ≥ 65 years. RESULTS: We identified 257 patients with an aMCC diagnosis, of whom 51% had stage IIIb disease and 49% had stage IV. Within 4 months after diagnosis, 84% of patients (n = 216) received treatment; 45% (n = 115) received surgery, 48% (n = 124) radiation therapy, and 31% (n = 80) chemotherapy. Second-line chemotherapy was administered in 33% of patients (n = 26) receiving first-line chemotherapy. Median overall survival was 27 months in patients whose aMCC was diagnosed at stage IIIb and 12 months in patients whose aMCC was diagnosed at stage IV. Median total 12-month direct healthcare costs were US$48,006 (25th-75th percentile range = US$30,594-US$69,797) per patient. Total costs were highest in patients receiving chemotherapy, either alone or combined with radiation and/or surgery (US$52,854; 25th-75th percentile range = US$34,473-US$71,987). CONCLUSION: Most patients with aMCC received initial treatment, including surgery, radiation, and/or chemotherapy, and approximately one-third of those receiving chemotherapy received second-line chemotherapy. Total 12-month direct healthcare costs were highest in patients who received chemotherapy alone or combined with radiation and/or surgery. These poor survival results and high treatment costs highlight the need for effective new aMCC therapies.

Budget impact model of avelumab in patients with metastatic merkel cell carcinoma in the US.

Objective: To estimate the budget impact of avelumab as a treatment option for patients with treatment-naïve first-line (1L) and previously treated second-line or later (2L+) metastatic Merkel cell carcinoma (mMCC) in the US. Methods: A budget impact model was developed to evaluate the addition of avelumab for the treatment of mMCC patients using a hypothetical 30 million-member US health plan over a 3-year time horizon (2019-2021). The comparator treatments included in the analysis were pembrolizumab and nivolumab (other immuno-oncology agents); and the chemotherapies routinely used in the eligible mMCC population. Model inputs included market share uptake of avelumab and other comparators, duration of treatments, and costs (drugs, health care resource utilization, adverse events). The model was evaluated from a commercial payer perspective. Sensitivity analyses were conducted to test uncertainties arising from the input values used in the model. Results: In a hypothetical commercial health plan of 30 million members, 285 patients with mMCC were identified over 3 years; 43 patients received avelumab as a 1L treatment over 3 years. In a world without avelumab, the total health care costs of treating patients with mMCC over 3 years were estimated to be US$11,710,115 from a commercial health plan perspective. With avelumab, there were estimated savings of $2,643,173 considering the total costs related to the treatment of mMCC over 3 years (23% reduction in the budget). The incremental cost per member per month over 3 years was -$0.0025. Conclusion: The model results indicate that the adoption of avelumab as a treatment option for mMCC would likely result in minimal budget impact from a US health plan perspective. Patients with mMCC, a rare condition with a poor prognosis and high unmet need, may benefit greatly from recently approved immunotherapies.

Travel burden associated with rare cancers: The example of Merkel cell carcinoma.

BACKGROUND: There are limited data on the travel burden for cancer patients with rare tumor types, such as Merkel cell carcinoma (MCC). OBJECTIVE: The objective of this study was to understand the travel burden of MCC patients. METHODS: This study used data from an MCC registry at the Seattle Cancer Care Alliance (SCCA). All MCC patients enrolled at SCCA with a valid 3-digit ZIP code were included. Patients were followed up from January 1, 2012 until their last follow-up, death, or end of data (January 1, 2017). Travel burden was measured by one-way travel distance to SCCA from each patient's 3-digit ZIP code. Patient demographics, tumor characteristics, and follow-up visit were evaluated and stratified by one-way driving distance of ≤300 and >300 miles. RESULTS: A total of 391 MCC patients were included (68% men, mean age = 67 years [±SD = ±11 years], 67% residing in the West, and 70% white). At diagnosis, 53% of the patients had Stage III or IV MCC. Mean one-way distance traveled by patients was 1,137 (median: 813) miles, and 57% of patients traveled >300 miles. Compared to patients who traveled ≤300 miles, those who traveled >300 miles were more likely to be <70 years old (46% vs 65%; P < 0.001), were diagnosed with advanced stage (III or IV) MCC (46% vs 59%; P = 0.01), had shorter follow-up in the cancer registry (mean: 509 vs 212 days; P < 0.001), and had fewer visits during follow-up (mean: 5.2 vs 2.5; P < 0.001). CONCLUSIONS: In this single cancer center study, the majority of MCC patients trav-eled long distances to receive expert care. Longer travel distances appeared to be associated with younger age, a more advanced stage of cancer at study entry and fewer in-clinic visits, suggesting that travel burden may impact timely and adequate patient care for this rare cancer.

Real-world comparison of bleeding risks among non-valvular atrial fibrillation patients prescribed apixaban, dabigatran, or rivaroxaban.

Limited real-world data are available regarding the comparative safety of non-vitamin K antagonist oral anticoagulants (NOACs). The objective of this retrospective claims observational cohort study was to compare the risk of bleeding among non-valvular atrial fibrillation (NVAF) patients prescribed apixaban, dabigatran, or rivaroxaban. NVAF patients aged ≥18 years with a 1-year baseline period were included if they were new initiators of NOACs or switched from warfarin to a NOAC. Cox proportional hazards modelling was used to estimate the adjusted hazard ratios of any bleeding, clinically relevant non-major (CRNM) bleeding, and major inpatient bleeding within 6 months of treatment initiation for rivaroxaban and dabigatran compared to apixaban. Among 60,227 eligible patients, 8,785 were prescribed apixaban, 20,963 dabigatran, and 30,529 rivaroxaban. Compared to dabigatran or rivaroxaban patients, apixaban patients were more likely to have greater proportions of baseline comorbidities and higher CHA2DS2-VASc and HAS-BLED scores. After adjusting for baseline clinical and demographic characteristics, patients prescribed rivaroxaban were more likely to experience any bleeding (HR: 1.35, 95% confidence interval [CI]: 1.26-1.45), CRNM bleeding (HR: 1.38, 95% CI: 1.27-1.49), and major inpatient bleeding (HR: 1.43, 95% CI: 1.17-1.74), compared to patients prescribed apixaban. Dabigatran patients had similar bleeding risks as apixaban patients. In conclusion, NVAF patients treated with rivaroxaban appeared to have an increased risk of any bleeding, CRNM bleeding, and major inpatient bleeding, compared to apixaban patients. There was no significant difference in any bleeding, CRNM bleeding, or inpatient major bleeding risks between patients treated with dabigatran and apixaban.

Using Response Evaluation Criteria in Solid Tumors in real-world evidence cancer research.

AIM: Real-world evidence of charted treatment responses to cancer drug therapy was compared with medical record derived radiographic measurements of target lesions per Response Evaluation Criteria in Solid Tumors (RECIST). MATERIALS & METHODS: 15 physicians treating 59 metastatic Merkel cell cancer (mMCC) patients contributed patient-level data. A comparison of medical record reported best response with radiographic measurements per RECIST of pre- and post-treatment target lesions. RESULTS: RECIST response rates were significantly lower compared with medical record reported with a concordance of 43.2% (95% CI: 28.0-58.4%). CONCLUSION: Subjective assessment of tumor response collected via traditional chart abstraction may overestimate benefit and limit the potential role of real-world evidence in value-based care research. The use of target lesion measurements presents an attractive alternative that better aligns with trial results.

Discontinuation risk comparison among 'real-world' newly anticoagulated atrial fibrillation patients: Apixaban, warfarin, dabigatran, or rivaroxaban.

Discontinuation of oral anticoagulants may expose non-valvular atrial fibrillation (NVAF) patients to an increased risk of stroke. This study describes the real-world discontinuation rates and compared the risk of drug discontinuation among NVAF patients initiating apixaban, warfarin, dabigatran, or rivaroxaban. This retrospective cohort study evaluated newly-anticoagulated NVAF patients in the MarketScan® data population from 01/01/2012 through 12/31/2014. Discontinuation was defined as a lack of subsequent prescription of the index drug within 30 days after the last supply day of the last prescription. A Cox model was used to estimate the hazard ratio (HR) of discontinuation, adjusted for age, sex, and comorbidities. Among 45,361 eligible NVAF patients, 15,461 (34.1%) initiated warfarin; 7,438 (16.4%) apixaban; 4,661 (10.3%) dabigatran; and 17,801 (39.2%) initiated rivaroxaban treatment. Compared to warfarin, patients who initiated dabigatran (adjusted HR [aHR]: 0.84, 95% confidence interval [CI]: 0.80-0.87, P<0.001), rivaroxaban (aHR: 0.70, 95% CI: 0.68-0.73, P<0.001), or apixaban (aHR: 0.57, 95% CI: 0.55-0.60, P<0.001) were 16%, 30%, and 43% less likely to discontinue treatment, respectively. When compared to apixaban, patients who initiated dabigatran (aHR: 1.46, 95% CI: 1.38-1.54, P<0.001) or rivaroxaban (aHR: 1.23, 95% CI: 1.17-1.28, P<0.001) were more likely to discontinue treatment. Among newly-anticoagulated NVAF patients in the real-world setting, initiation on rivaroxaban, dabigatran, or apixaban was associated with a significantly lower risk of discontinuation compared to warfarin. When compared to apixaban, patients who initiated treatment with warfarin, dabigatran, or rivaroxaban were more likely to discontinue treatment.

Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma.

AIM: Merkel cell carcinoma (MCC) is a rare neuroendocrine, cutaneous malignancy with poor prognosis once metastasized. The aim of this study was to conduct a systematic literature review to assess clinical outcomes associated with chemotherapy regimens in metastatic MCC. MATERIALS & METHODS: Embase®, MEDLINE®, MEDLINE®-In-Process and CENTRAL were searched for studies published in January 2016. RESULTS & CONCLUSION: Overall, the literature on chemotherapy in patients with metastatic MCC is sparse, with most studies being case series/reports. Across all studies, response rates ranged from 20 to 61%, with higher response rates in first-line setting (53-61%) versus second-line setting (23-45%). Among responders, duration of response was short (≤8 months) in both first- and second-line settings. There is a need for novel agents that can induce durable responses in metastatic MCC.

Major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin: a "real-world" observational study in the United States.

BACKGROUND: Limited data are available about the real-world safety of non-vitamin K antagonist oral anticoagulants (NOACs). OBJECTIVES: To compare the major bleeding risk among newly anticoagulated non-valvular atrial fibrillation (NVAF) patients initiating apixaban, warfarin, dabigatran or rivaroxaban in the United States. METHODS AND RESULTS: A retrospective cohort study was conducted to compare the major bleeding risk among newly anticoagulated NVAF patients initiating warfarin, apixaban, dabigatran or rivaroxaban. The study used the Truven MarketScan(®) Commercial & Medicare supplemental US database from 1 January 2013 through 31 December 2013. Major bleeding was defined as bleeding requiring hospitalisation. Cox model estimated hazard ratios (HRs) of major bleeding were adjusted for age, gender, baseline comorbidities and co-medications. Among 29 338 newly anticoagulated NVAF patients, 2402 (8.19%) were on apixaban; 4173 (14.22%) on dabigatran; 10 050 (34.26%) on rivaroxaban; and 12 713 (43.33%) on warfarin. After adjusting for baseline characteristics, initiation on warfarin [adjusted HR (aHR): 1.93, 95% confidence interval (CI): 1.12-3.33, P=.018] or rivaroxaban (aHR: 2.19, 95% CI: 1.26-3.79, P=.005) had significantly greater risk of major bleeding vs apixaban. Dabigatran initiation (aHR: 1.71, 95% CI: 0.94-3.10, P=.079) had a non-significant major bleeding risk vs apixaban. When compared with warfarin, apixaban (aHR: 0.52, 95% CI: 0.30-0.89, P=.018) had significantly lower major bleeding risk. Patients initiating rivaroxaban (aHR: 1.13, 95% CI: 0.91-1.41, P=.262) or dabigatran (aHR: 0.88, 95% CI: 0.64-1.21, P=.446) had a non-significant major bleeding risk vs warfarin. CONCLUSION: Among newly anticoagulated NVAF patients in the real-world setting, initiation with rivaroxaban or warfarin was associated with a significantly greater risk of major bleeding compared with initiation on apixaban. When compared with warfarin, initiation with apixaban was associated with significantly lower risk of major bleeding. Additional observational studies are required to confirm these findings.

Pharmacological Prophylaxis for Venous Thromboembolism Among Hospitalized Patients With Acute Medical Illness: An Electronic Medical Records Study.

Patients hospitalized with acute medical illness have an elevated risk of venous thromboembolism (VTE). American College of Chest Physicians guidelines list various chronic illnesses, sepsis, advanced age, history of VTE, and immobility as risk factors and recommend prophylactic anticoagulation using fondaparinux, low-molecular weight heparin, or low-dose unfractionated heparin. The objectives of this study were to examine pharmacological prophylaxis against VTE among hospitalized medically ill patients and to assess demographic and clinical correlates related to VTE prophylaxis. A retrospective (1999-2010) electronic medical records study included patients aged 40 years and older hospitalized for at least 3 days, with significant medical illness or with a VTE hospitalization 30-365 days before admission. Each patient's first qualifying hospitalization was analyzed. Exclusions were if VTE treatment was started within 1 day of admission, or if warfarin (and not heparin or enoxaparin) was used. Prophylaxis was defined if the first inpatient dose of subcutaneous heparin or enoxaparin was at prophylaxis levels (lower than treatment levels). Multivariable logistic regression was used to examine factors associated with VTE prophylaxis. Among 12,980 patients, 22.1% received prophylaxis (11.8% with enoxaparin, 10.3% with heparin). VTE prophylaxis was positively associated with year of hospitalization, subcutaneous heparin in the month before admission, aspirin, self-pay status, age, and sepsis. VTE prophylaxis was negatively associated with smoking, alcohol, warfarin in the past 30 days, and primary diagnoses of stroke, infectious disease, or inflammatory bowel disease. Pharmacological VTE prophylaxis has increased significantly over the past 12 years but is still largely underused in patients hospitalized with acute medical illness. Multiple demographic, behavioral, and clinical factors are associated with inpatient VTE prophylaxis.