Hypertension treatment for patients receiving ibrutinib: a multicenter retrospective study.

ABSTRACT: Although Bruton tyrosine kinase inhibitors (BTKis) are generally well tolerated and less toxic than chemotherapy alternatives used to treat lymphoid malignancies, BTKis like ibrutinib have the potential to cause new or worsening hypertension (HTN). Little is known about the optimal treatment of BTKi-associated HTN. Randomly selected patients with lymphoid malignancies on a BTKi and antihypertensive drug(s) and with at least 3 months of follow-up data were sorted into 2 groups: those diagnosed with HTN before BTKi initiation (prior-HTN), and those diagnosed with HTN after BTKi initiation (de novo HTN). Generalized estimating equations assessed associations between time varying mean arterial pressures (MAPs) and individual anti-HTN drug categories. Of 196 patients included in the study, 118 had prior-HTN, and 78 developed de novo HTN. Statistically significant mean MAP reductions were observed in patients with prior-HTN who took ß blockers (BBs) with hydrochlorothiazide (HCTZ), (-5.05 mmHg; 95% confidence interval [CI], 10.0 to -0.0596; P = .047), and patients diagnosed with de novo HTN who took either an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) with HCTZ (-5.47 mmHg; 95% CI, 10.9 to -0.001; P = .05). These regimens also correlated with the greatest percentages of normotensive MAPs. Treatment of HTN in patients taking a BTKi is challenging and may require multiple antihypertensives. Patients with prior-HTN appear to benefit from combination regimens with BBs and HCTZ, whereas patients with de novo HTN appear to benefit from ACEi/ARBs with HCTZ. These results should be confirmed in prospective studies.

Results from a Real-World Multicenter Analysis of 482 Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib: A Look at Racial Differences.

BACKGROUND: Despite recent approvals of lifesaving treatments for chronic lymphocytic leukemia (CLL), real-world data on the tolerability of the Bruton tyrosine kinase inhibitor ibrutinib for CLL treatment are lacking, especially in Black patients. OBJECTIVE: To expand upon a previously reported retrospective chart review of ibrutinib-treated patients with CLL to increase the number of sites and the enrollment period in first-line (1L) and relapsed/refractory (R/R) settings with a subanalysis based on ethnicity. PATIENTS AND METHODS: Adults with CLL who initiated ibrutinib treatment from five centers were followed for ≥ 6 months. RESULTS: We identified 482 patients with CLL [405 White (153 1L, 252 R/R), 37 Black (17 1L, 20 R/R), 40 other/unidentified]. At baseline, 58.5% of all patients (68.8% of Black patients) had hypertension. At a median follow-up of 28.2 months, 31.1% of patients overall discontinued ibrutinib, 16.2% due to adverse events (12.2% 1L, 18.8% R/R). Overall, 46.0% of patients experienced ≥ 1 dose hold (40.2% 1L, 49.8% R/R), and 28.8% of patients experienced ≥ 1 dose reduction (24.9% 1L, 31.4% R/R). Among Black patients, ibrutinib was discontinued in 24.3% of patients (17.6% 1L, 30.0% R/R), 8.1% due to disease progression and 5.4% due to adverse events; 40.5% of patients experienced ≥ 1 dose hold (35.3% 1L, 45.0% R/R), and 32.4% of patients experienced ≥ 1 dose reduction (23.5% 1L, 40.0% R/R). CONCLUSIONS: Toxicity and disease progression were the most common reasons for ibrutinib discontinuations in the overall population and among Black patients, respectively. Encouraging research participation of underrepresented patient groups will help clinicians better understand treatment outcomes.

Ibrutinib, a Bruton tyrosine kinase inhibitor, is an approved oral targeted therapy for the treatment of chronic lymphocytic leukemia (CLL). Patients treated with ibrutinib can experience side effects (referred to as adverse events) and may need to reduce the drug dose (referred to as dose reductions) or stop treatment (referred to as discontinuations) for a variety of reasons. A previous study showed that patients who were treated with ibrutinib experienced frequent dose reductions and discontinuations. This study described dose reductions and discontinuations in a larger patient population treated with ibrutinib and also described outcomes in Black patients. Patients with CLL treated with ibrutinib were identified from five medical centers and were followed for a minimum of 6 months. Patients experienced frequent dose reductions and discontinuations in routine clinical practice. The most common cause of discontinuations was adverse events in the overall patient population and disease progression in the Black patient population. Black patients treated with ibrutinib had similar rates of dose reductions and discontinuations as the overall patient population. Rates of dose reductions and discontinuations for patients with CLL treated with ibrutinib were higher in this real-world study than in clinical trials.

Real-world comparative effectiveness of acalabrutinib and ibrutinib in patients with chronic lymphocytic leukemia.

Novel agents, including Bruton tyrosine kinase inhibitors (BTKis), have become the standard of care for patients with chronic lymphocytic leukemia (CLL). We conducted a real-world retrospective analysis of patients with CLL treated with acalabrutinib vs ibrutinib using the Flatiron Health database. Patients with CLL were included if they initiated acalabrutinib or ibrutinib between 1 January 2018 and 28 February 2021. The primary outcome of interest was time to treatment discontinuation (TTD). Kaplan-Meier analysis was used to estimate unweighted and weighted median TTD. A weighted Cox proportional hazards model was used to compare the TTD between cohorts. Of the 2509 patients included in the analysis, 89.6% received ibrutinib, and 14.1% received acalabrutinib. TTD was not significantly different between cohorts in the unweighted analysis. After weighting, the cohorts were balanced on all baseline characteristics except cardiovascular risk factors and baseline medications use. The median (95% confidence interval [CI]) TTD was not reached (NR; 95% CI, 25.1 to NR) for the acalabrutinib cohort and was 23.4 months (95% CI, 18.1-28.7) for the ibrutinib cohort. The discontinuation rate at 12 months was 22% for the weighted acalabrutinib cohort vs 31% for the weighted ibrutinib cohort (P = .005). After additional adjustment for prior BTKi use, the acalabrutinib cohort had a 41% lower risk of discontinuation vs ibrutinib (hazard ratio, 0.59; 95% CI, 0.43-0.81; P = .001). In the largest available study comparing BTKis, patients with CLL receiving acalabrutinib demonstrated lower rates of discontinuation and a prolonged time to discontinuation vs those receiving ibrutinib.

Time and personnel costs associated with adverse event (AE) management among patients with chronic lymphocytic leukemia (CLL).

OBJECTIVES: Novel therapies improve clinical outcomes in chronic lymphocytic leukemia (CLL), although adverse event (AE) profiles differ. This study evaluated time and personnel costs of AE management among healthcare professionals (HCPs) treating patients with CLL with novel therapies. METHODS: A non-interventional prospective survey was conducted over 2 months. Eligible HCPs reported the time per day spent performing AE management activities for CLL patients treated with acalabrutinib, ibrutinib, or venetoclax. Mean time and personnel costs (USD) per activity were summarized and used to estimate the total annual costs of AE management for an average-sized oncology practice. RESULTS: For an average-sized practice (28 HCPs with an average of 56 CLL patients), the mean annual personnel cost of AE management for CLL patients on novel agents was estimated at $115,733. The personnel cost associated with acalabrutinib ($20,912) was less than half that of ibrutinib ($53,801) and venetoclax ($41,884), potentially due to fewer severe AEs and less time spent by oncologists managing AEs compared to other HCP types. CONCLUSION: The substantial burden of AE management for patients with CLL may vary by treatment used. Acalabrutinib was associated with lower annual costs of AE management at an oncology practice level compared to ibrutinib and venetoclax.

Cost-effectiveness of acalabrutinib regimens in treatment-naïve chronic lymphocytic leukemia in the United States.

BACKGROUND: Clinical outcomes in chronic lymphocytic leukemia (CLL) have improved with targeted therapy, including Bruton tyrosine kinase inhibitors such as acalabrutinib. METHODS: A semi-Markov model with three health states (progression-free, progressed disease, and death) estimated cost per quality-adjusted life-year (QALY) gained for acalabrutinib ± obinutuzumab vs chlorambucil + obinutuzumab in treatment-naive CLL (based on ELEVATE-TN). The model used direct costs and resource utilization from the US Medicare perspective and utility values sourced from literature. Sensitivity analyses tested the robustness of the model. RESULTS: Over a 30-year lifetime horizon, the model base case analysis suggested that acalabrutinib monotherapy had an incremental cost of $206,329 and 2.52 QALYs gained versus chlorambucil + obinutuzumab, resulting in an incremental cost-effectiveness ratio (ICER) of $81,960/QALY. Acalabrutinib + obinutuzumab had an incremental cost of $423,747 and 2.79 QALYs gained (ICER: $152,153/QALY). Probabilistic sensitivity analysis showed the probability of acalabrutinib monotherapy being cost-effective as 59% to 73% at a $100,000-to-150,000/QALY willingness-to-pay threshold; the probability of acalabrutinib + obinutuzumab being cost-effective ranged from 34% to 51%. CONCLUSIONS: Although the analysis is limited by uncertainty in postprogression survival outcomes, acalabrutinib monotherapy is likely cost-effective vs chlorambucil + obinutuzumab in treatment-naive CLL in the US Medicare setting.

Health disparity in use of novel agents for first-line therapy in Black and White patients with chronic lymphocytic leukemia in the Department of Veterans Affairs.

BACKGROUND: Novel agents (NAs) (ibrutinib, idelalisib, and venetoclax) were first introduced in 2013 as therapeutic options to treat chronic lymphocytic leukemia (CLL). OBJECTIVES: To determine if the uptake of NAs for first-line treatment was similar in Black and White patients with CLL treated in the Department of Veterans Affairs (VA). METHODS: We conducted a retrospective cohort study including adults with CLL managed in the VA from October 1, 2013, to September 30, 2017. Descriptive statistics were used to summarize demographic data, and appropriate bivariable statistical tests were used to compare NA use, baseline characteristics, health outcomes, and complications. A multivariable logistic regression model was used to identify factors associated with uptake of NAs. The study included 565 patients; 86% were White and 14% were Black. Black patients were younger than White patients (median age [66 vs 69 years; P < 0.01]) but had similar median baseline Charlson comorbidity scores (4 vs 5). RESULTS: Overall, Black patients were less likely to receive NAs than White patients (14% vs 26%; P = 0.02). The gap narrowed over the study period: 4% vs 17% (2014), 13% vs 25% (2015), 17% vs 33% (2016), and 31% vs 33% (2017). Black race (P = 0.02) and fiscal year (P < 0.01) were the only variables significantly associated with NA use in the multivariable model. Health outcomes and most complications were similar for Black and White patients despite the difference in prescribing patterns. CONCLUSIONS: This is the first study to identify a potential health disparity with respect to use of NAs among Black and White patients with CLL treated in the VA. Fortunately, health outcomes and most complications were similar for Black and White patients despite the difference in prescribing patterns. DISCLOSURES: Funding for the study was provided by AstraZeneca as a research grant to the Foundation for Advancing Veterans' Health Research (FAVHR), a non-profit entity within the Audie L. Murphy Veterans Hospital, San Antonio, TX. Drs Nooruddin and Frei have received research grants (paid to FAVHR) from AstraZeneca in the last 3 years. Ms Ryan is an employee of AstraZeneca. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the National Institutes of Health, or the authors' affiliated institutions.

Real-world ibrutinib dose reductions, holds and discontinuations in chronic lymphocytic leukemia.

Aim: A retrospective chart review of ibrutinib-treated patients with chronic lymphocytic leukemia (CLL) was conducted. Patients & methods: Adults with CLL who initiated ibrutinib were followed for ≥6 months (n = 180). Results: Twenty-five percent of first-line ibrutinib patients experienced ≥1 dose reduction, mainly due to adverse events (AEs; 79%). Treatment discontinuations and dose holds occurred in 20 and 34% of patients, respectively, most commonly due to AEs (73 and 74%). Approximately one-quarter of relapsed/refractory ibrutinib patients experienced ≥1 dose reduction, mainly due to AEs (88%). Treatment discontinuation and dose holds occurred in 40% of patients (58 and 76% due to AEs, respectively). Conclusion: Dose reductions, holds and discontinuations were frequent in patients with CLL receiving ibrutinib in routine clinical practice.

Lay abstract Chronic lymphocytic leukemia (CLL) is a cancer that develops from a type of white blood cells called 'B cells.' Ibrutinib is a targeted therapy that inhibits the activity of a protein called Bruton's tyrosine kinase, which plays a key role in CLL. Patients receiving ibrutinib treatment can experience side effects ('adverse events'). In addition, patients may need to reduce their drug dose ('dose reductions') or stop treatment ('discontinuations') for a variety of reasons. We reviewed patients' charts to describe dose reductions and discontinuations in ibrutinib-treated patients with CLL. Our results indicate that dose reductions and discontinuations were frequent in patients with CLL receiving ibrutinib in routine clinical practice, and that the most common reason was adverse events.

Outcomes in chronic lymphocytic leukemia patients on novel agents in the US Veterans Health Administration System.

The US veteran population has a high proportion of chronic lymphocytic leukemia (CLL) risk factors. Using the Veterans Health Administration (VHA) population, we conducted a retrospective chart review of 1205 CLL patients who initiated treatment with a novel oral agent. For 1L ibrutinib, 33% (n = 107) discontinued therapy during the study, of which 64% discontinued due to adverse events (AEs). For relapsed/refractory (R/R) ibrutinib, 35% (n = 262) discontinued therapy, of which 63% discontinued due to AEs. For R/R venetoclax, 31% (n = 27) discontinued therapy, of which 41% were due to AEs. For idelalisib, 84% (n = 41) discontinued therapy, of which 54% were due to AEs. This real-world study suggests that AEs play an important role in dose reductions and discontinuations; however, physician inexperience in using these drugs when they were first introduced could be part of what is leading to these negative outcomes.

Oncologist and Patient Preferences for Novel Agents in First-Line Treatment for Chronic Lymphocytic Leukemia: Commonalities and Disconnects.

PURPOSE: Treatment for chronic lymphocytic leukemia (CLL) has changed dramatically with the approval of novel agents. Information regarding how patients and oncologists make trade-offs across attributes of novel therapies is limited. The purpose of this study was to understand how variations in attributes impact treatment choice among patients and oncologists. PATIENTS AND METHODS: In this study, 371 participants (patients [n=220] and oncologists [n=151]) completed an online discrete choice experiment (DCE) to quantify preferences for first-line (1L) CLL treatment with novel agents; participants chose between hypothetical treatment profiles consisting of eight attributes with varying levels taken from published literature. Hierarchical Bayesian models were used to estimate attribute level preference weights. The weights were used to compute relative importance, a measure of how influential an attribute is to treatment choice. RESULTS: Increasing 2-year progression-free survival (PFS) from 75% to 95% had the greatest impact on preferences in 1L CLL treatment, accounting for 40% and 30% of the variation in preferences among patients and oncologists, respectively. Risk differences in atrial fibrillation (AF), infection, and discontinuation due to adverse events (AEs) were also important to patients and oncologists. Among both groups, risk differences in tumor lysis syndrome (TLS) and bleeding were least influential in treatment choice. Oncologists required 2-4 times higher increases in 2-year PFS than patients to accept increased risks of AF, discontinuation due to AEs, bleeding, TLS, and arthralgia/myalgia. CONCLUSION: Patient-oncologist communication may be improved by a more focused discussion on the risks of AEs, relative to treatment outcomes, with patient goals in mind.

Real-World Costs of Adverse Events in First-Line Treatment of Metastatic Non-Small Cell Lung Cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer in the United States. Immunotherapies and cytotoxic chemotherapies used to treat advanced NSCLC carry a substantial risk of adverse events (AEs), but real-world data on the incidence and costs associated with the unique AE profiles of these treatments are sparse. OBJECTIVE: To examine the AE incidence and costs among patients initiating non-driver mutation-targeted first-line therapy for metastatic NSCLC (mNSCLC) in clinical practice. METHODS: This was a retrospective administrative claims study conducted among commercial and Medicare Advantage health plan members who initiated first-line, nontargeted systemic anti-NSCLC therapy between January 1, 2008, and February 28, 2018. Patients were assigned to mutually exclusive treatment cohorts (cytotoxic chemotherapy [CHEM], immuno-oncology agents [IO], or immuno-oncology + cytotoxic chemotherapy [IO-CHEM]) and were observed from the index date (start of first-line therapy) through the earliest of health plan disenrollment, death, or March 31, 2018. AE incidence rates and associated health care costs were measured from the index date through the earliest of the start of a new therapy, 180 days after the end of first-line therapy, or the end of the study period. The factors influencing whether patients incurred high AE-related health care costs were assessed using multivariable models adjusted for patient demographic and clinical characteristics. RESULTS: The final study population (mean [SD] age 68.6 [9.5] years, 53.9% male) included 8,818 in the CHEM cohort, 482 in the IO cohort, and 412 in the IO-CHEM cohort. Overall, 74.4% had at least 1 AE during follow-up. The AE incidence rate was lowest for the IO cohort, with incidence rate ratios (95% CI) of 1.4 (1.3-1.6) for the CHEM cohort and 1.4 (1.2-1.6) for the IO-CHEM cohort. Mean AE-related costs were lowest for the IO cohort ($16,319) and highest for the CHEM cohort ($23,009; P < 0.001). In the multivariable analysis, the odds of incurring any AE costs were similar for the IO and IO-CHEM cohorts compared with the CHEM cohort (OR = 0.82; P = 0.135 and OR = 0.98; P = 0.888, respectively). Among patients who incurred AE costs, those in the IO cohort were less likely than those in the CHEM cohort to have high costs (OR = 0.60; P = 0.030); the difference between the IO-CHEM and CHEM cohorts was not statistically significant. CONCLUSIONS: Among real-world patients initiating nontargeted first-line therapy for mNSCLC, those receiving immunotherapy experienced fewer AEs and had lower total AE-related costs than those treated with cytotoxic chemotherapy. Immunotherapy-treated patients were no more likely than chemotherapy-treated patients to incur AE-related costs and were less likely to have high AE costs if they incurred any at all. These findings indicate that immunotherapy-related AEs are not a differentiating factor in cost of care for this patient population in clinical practice. DISCLOSURES: This study was sponsored by AstraZeneca. Ryan is an employee of AstraZeneca. Engel-Nitz, Johnson, and Bunner are employees of Optum, which was contracted by AstraZeneca to conduct this study, and shareholders in UnitedHealth Group. Engel-Nitz has also worked on cancer-related studies for which Optum received funding from Bayer AG, Clovis Oncology, Eli Lilly, EMD Serono, Exact Sciences, Janssen, and Novartis. Johnson worked on cancer-related studies for which Optum received funding from Eli Lilly, Medtronic, Sanofi, and UnitedHealthcare. Bunner has worked on cancer-related studies for which Optum received funding from Celgene and Incyte.

Long-term survival trends in patients with unresectable stage III non-small cell lung cancer receiving chemotherapy and radiation therapy: a SEER cancer registry analysis.

BACKGROUND: To evaluate the value of new therapies for non-small cell lung cancer (NSCLC), it is necessary to understand overall survival (OS) rates associated with previous standard therapies and how these rates have evolved over time. METHODS: We retrospectively analyzed data from patients enrolled in the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Adults with unresectable, stage III NSCLC treated with chemoradiotherapy were grouped by diagnosis year (2000-2002; 2003-2005; 2006-2008; 2009-2011; 2012-2013). The primary endpoint was OS (data cut-off, December 31, 2014), estimated using the Kaplan-Meier estimator. Temporal survival-trend significance was tested using a two-sided log-rank trend test. RESULTS: Of 12,865 eligible patients, 59.1% were male, 59.9% had stage IIIB disease, and 62.7% had non-squamous histology. Median age at diagnosis was 67 years. Overall, 10,899 (84.7%) patients died and 1966 (15.3%) were censored/lost to follow-up. Median follow-up (95% confidence interval [CI]) was 80 (77-82) months; median OS (95% CI) was 15 (15-16) months; 1- and 3-year survival probabilities (95% CI) were 57.7% (56.9-58.6) and 24.1% (23.3-24.8), respectively. Stratification by diagnosis year showed consistent improvements in survival over time (p < 0.0001 for trend). Median OS was 12, 14, 15, 18, and 19 months in successive cohorts. CONCLUSIONS: OS in patients diagnosed with unresectable, stage III NSCLC between 2003 and 2013 was consistent with that from clinical studies of sequential/concurrent chemoradiotherapy. Despite improvement over time, median OS was < 2 years and mortality remained high during the first year post-diagnosis.

Predictors of chemoradiotherapy versus single modality therapy and overall survival among patients with unresectable, stage III non-small cell lung cancer.

INTRODUCTION: Concurrent chemoradiotherapy (cCRT) was the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) prior to the PACIFIC trial, however, patients also received single modality therapy. This study identified predictors of therapy and differences in overall survival (OS). METHODS: This retrospective study included stage III NSCLC patients aged ≥65 years, with ≥1 claim for systemic therapy (ST) or radiotherapy (RT) within 90 days of diagnosis, identified in SEER-Medicare data (2009-2014). Patients who had overlapping claims for chemotherapy and RT ≤90 days from start of therapy were classified as having received cCRT. Patients who received sequential CRT or surgical resection of tumor were excluded. Predictors of cCRT were analyzed using logistic regression. OS was compared between therapies using adjusted Cox proportional hazards models. RESULTS: Of 3,799 patients identified, 21.7% received ST; 26.3% received RT; and 52.0% received cCRT. cCRT patients tended to be younger (p <0.001), White (p = 0.002), and have a good predicted performance status (p<0.001). Patients who saw all three specialist types (medical oncologist, radiation oncologist, and surgeon) had increased odds of receiving cCRT (p<0.001). ST and RT patients had higher mortality risk versus cCRT patients (hazard ratio [95% CI]: ST: 1.38 [1.26-1.51]; RT: 1.75 [1.61, 1.91]); p<0.001). CONCLUSIONS: Several factors contributed to treatment selection, including patient age and health status, and whether the patient received multidisciplinary care. Given the survival benefit of receiving cCRT over single-modality therapy, physicians should discuss treatment within a multidisciplinary team, and be encouraged to pursue cCRT for patients with unresectable stage III NSCLC.

Real-world incidence and cost of pneumonitis post-chemoradiotherapy for Stage III non-small-cell lung cancer.

Aim: To estimate the real-world incidence and timing of radiation pneumonitis following chemoradiotherapy for Stage III non-small-cell lung cancer and compare costs between patients with and without radiation pneumonitis. Methods: Retrospective analysis using the Symphony Health Integrated Dataverse. Results: Pneumonitis incidence was 12.4% with a 177-day mean time to onset. Patients with versus without pneumonitis were more frequently admitted to the hospital (33.8 vs 19.2%, p < 0.0001) and seen in the emergency room (51.9 vs 35.8%, p < 0.0001) and had higher mean total healthcare costs (US$4251 vs US$3969 per-patient per-month; p = 0.0163). Conclusion: Although pneumonitis significantly increased healthcare resource utilization and costs in chemoradiotherapy-treated Stage III non-small-cell lung cancer, the per-patient per-month differential was <10%. Such financial assessments are critical for cost-benefit analysis.

Treatment patterns and overall survival among patients with unresectable, stage III non-small-cell lung cancer.

Aim: To analyze treatment patterns and overall survival (OS) across time (2009-2014) among patients with unresected, stage III non-small-cell lung cancer (NSCLC). Patients & methods: Stage III NSCLC patients aged ≥65 years who initiated therapy were identified using SEER-Medicare data. Results: Among 4564 patients, 84% received chemotherapy (with or without radiotherapy), and 59% received chemoradiotherapy (CRT). Carboplatin + paclitaxel was the most frequent regimen. Median (interquartile range) OS among chemotherapy patients was 13.2 (6.0-28.9) months, and 14.8 (6.7-33.4) months among CRT patients. Among CRT patients, there was no difference in OS across years of CRT initiation. Conclusion: OS remained static across 2009-2014, indicating stagnancy in clinical outcomes for stage III NSCLC patients and a need for more effective therapeutic options.

Real-world treatment patterns among patients with unresected stage III non-small-cell lung cancer.

Aim: Little is known about recent treatment patterns among patients with unresected stage III NSCLC in the real world. This retrospective study used medical records from USA community oncology practices to address this knowledge gap. Materials & methods: Eligible patients were stage III NSCLC adults diagnosed between 1 January 2011 and 1 March 2016 without surgical resection. Treatment patterns were assessed across three progression intervals, from stage III diagnosis through third progression. Results: The most common regimen in interval 1 was platinum doublet chemotherapy + radiation therapy, in interval 2 was chemotherapy only, and in interval 3 was non-platinum chemotherapy monotherapy. Conclusion: Most patients were treated following national guidelines, but important unmet needs remain.

Real-world outcomes in patients with unresected stage III non-small cell lung cancer.

This study examined real-world clinical outcomes such as progression-free survival (PFS), time to metastasis (TTM), overall survival (OS), and health-related quality of life (HRQOL) in patients with unresected stage III non-small cell lung cancer (NSCLC) treated in the community setting. A retrospective review of medical records extracted from 10 US community oncology practices was conducted. Eligible patients were adults diagnosed with stage III NSCLC from 1/1/2011 to 3/1/2016 without evidence of surgical resection within 6 months after stage III NSCLC diagnosis (index date). PFS, OS, and TTM were assessed from the index date, and were analyzed using Kaplan-Meier and Cox regression analyses. HRQOL was assessed for a subset of patients using a patient-reported measure, the 86-item Patient Care Monitor (PCM). Linear mixed models (LMM) were used to assess the impact of patient characteristics and change in PCM scores associated with progression. Among the sample of 478 patients, median PFS (95% confidence interval) was 10 months (9-11), median OS was 20 months (17-22), and median TTM was 30 months (23-45). Most patients (58.2%) experienced disease progression, which the LMM showed to be associated with significant worsening of physical symptoms and psychological states (p < 0.001). This study documented PFS and OS consistent with published literature. The majority of patients experienced disease progression, which was associated with worsening of HRQOL. These findings highlighted the need for better therapeutic options in patients with unresected stage III NSCLC with potential to improve patient outcomes and HRQOL.

The comparative economic burden of mild, moderate, and severe fibromyalgia: results from a retrospective chart review and cross-sectional survey of working-age U.S. adults.

BACKGROUND: Patients with fibromyalgia report persistent widespread pain, fatigue, and substantial functional limitations, which may lead to high health resource use (HRU) and lost productivity. Previous analyses of the U.S. population have not examined the direct and indirect costs of fibromyalgia by severity level. OBJECTIVES: To assess (a) HRU, direct and indirect costs associated with fibromyalgia in routine clinical practice in the United States using a patient-centric approach, and (b) the relationship of fibromyalgia severity level to HRU and costs. METHODS: This study recruited a nonprobability convenience sample of 203 subjects aged 18 through 65 years between August 2008 and February 2009 from 20 U.S. community-based physician offices. Subjects had a prior diagnosis of fibromyalgia by a rheumatologist, neurologist, or pain specialist; received treatment at the enrolling physician's practice for at least 3 months; experienced widespread pain for at least 3 months; and experienced pain in the previous 24 hours. Subjects completed a 106-item patient questionnaire that included 5 validated health-related quality-of-life instruments and study-specific questions about demographics; clinical history; overall health; treatment satisfaction; and impact of fibromyalgia on cognitive function, daily activities, and employment status. Subjects also self-reported hours of unpaid informal caregiver time because of inability to perform daily activities (e.g., housework, child care), out-of-pocket expenses for medical and nonmedical services, and lost productivity related to fibromyalgia for the previous 4 weeks. The 20-item Fibromyalgia Impact Questionnaire total score was used to stratify subjects into fibromyalgia severity groups (0 to less than 39 = mild, 39 to less than 59 = moderate, 59 to 100 = severe). Staff at each site recorded clinical characteristics, HRU, and medication use attributable to fibromyalgia on a paper clinical case report form (CRF) based on a 3-month retrospective medical chart review. Unit costs for 2009 were assigned to the 3-month HRU data reported on the CRF and 4-week subject-reported lost productivity. Costs were then annualized and reported in the following categories: direct medical, direct nonmedical, and indirect. Differences across severity levels were evaluated using the Kruskal-Wallis test (continuous measures) and Pearson chi-square or Fisher's exact tests (categorical measures) at the 0.05 alpha level. RESULTS: Of the 203 subjects, 21 (10.3%) had mild, 49 (24.1%) had moderate, and 133 (65.5%) had severe fibromyalgia. For subjects with mild, moderate, and severe fibromyalgia, respectively, the number of fibromyalgia-related medications (3-month means: 1.8, 2.3, and 2.8, P = 0.011) and office visits to health care providers (3-month means: 2.7, 5.2, and 6.9, P < 0.001) significantly differed across severity levels. Across severity levels, total medical and nonmedical out-of-pocket costs also differed (P = 0.025). Mean [median] 3-month total direct costs (including payer costs for HRU and out-of-pocket costs for medical and nonmedical services) were $1,213 [$1,150], $1,415 [$1,215], and $2,329 [$1,760] for subjects with mild, moderate, and severe fibromyalgia, respectively (P = 0.002); and mean [median] 3-month indirect costs (including subject-reported absenteeism, unemployment, disability, and the estimated value of unpaid informal care) were $1,341 [$0], $5,139 [$1,680], and $8,285 [$7,030] (P < 0.001). Mean total indirect costs accounted for 52.5%, 78.4%, and 78.1% of mean total costs for subjects with mild, moderate, and severe fibromyalgia, respectively. CONCLUSIONS: Direct and indirect costs related to fibromyalgia are higher among subjects with worse fibromyalgia severity. Indirect costs account for a majority of fibromyalgia-related costs at all fibromyalgia severity levels.

Impact of fibromyalgia severity on health economic costs: results from a European cross-sectional study.

BACKGROUND: Fibromyalgia (FM) is a chronic disorder characterized by persistent and widespread pain, often accompanied with fatigue, sleep disturbance and other symptoms. FM affects a population mostly of a productive age and is thus associated with significant lost productivity and disability, in addition to healthcare costs for medications and physician office visits. While other studies have examined FM costs in Europe, few, if any, have examined cost by FM severity level. OBJECTIVE: The objective of this study was to examine health resource utilization (HRU) and costs associated with FM in routine clinical practice in France and Germany across disease severity levels. METHODS: A total of 299 patients with FM, previously diagnosed by a rheumatologist, were recruited from physician offices in France and Germany during routine visits. Subjects completed questions about their pain, health-related quality of life, treatment satisfaction, productivity and FM-related out-of-pocket expenses; site staff recorded clinical, treatment and HRU information for the previous 3 months based on a review of medical records. FM severity was defined using subjects' Fibromyalgia Impact Questionnaire (FIQ) total scores. Annual costs from a societal perspective were calculated in €, year 2008 values, and included direct costs (e.g. physician office visits, medications, out-of-pocket expenses) and indirect costs (e.g. missed days of work and lost productivity). The mean annual costs were calculated based on 3-month data. RESULTS: Subjects were reported to have a mean (SD) of 2.9 (1.9) physician office visits in France and 4.9 (3.2) visits in Germany over the past 3 months, corresponding to an average of 11.6 and 19.6 visits a year, respectively. A total of 91% of subjects were receiving prescription medication for their FM. French subjects reported a lower use of anti-inflammatories (39% of subjects) and a higher use of other analgesics (59% of subjects) than German subjects (67% and 34%, respectively). Subjects in full- or part-time employment reported missing a mean (SD) of 2.7 (6.0) days of work due to FM in France and 2.1 (3.8) days in Germany over the last 4 weeks (corresponding to 32.4 and 25.2 days of work missed due to FM per year in France and Germany, respectively). In France, total costs were €7900 (direct €910, indirect €6990). In Germany, total costs were €7256 (direct €1765, indirect €5491). A trend of higher total costs was seen as FM severity increased; however, the results were significant (p = 0.003) only for Germany. CONCLUSIONS: FM imposes a significant economic burden on society. Consistent with other studies, FM subjects were found to have substantial costs, over 75% of which were driven by indirect costs from lost productivity. These costs increased as FM severity increased, resulting in a more than 200% difference in cost between mild and severe FM. Overall FM costs were similar between France and Germany; although lost productivity accounted for a higher proportion of costs in France.

Clinical and economic outcomes in Medicare beneficiaries with stage 3 or stage 4 chronic kidney disease and anemia: the role of intravenous iron therapy.

BACKGROUND: Anemia in patients with chronic kidney disease (CKD) is associated with increased morbidity and mortality, decreased quality of life, and substantial health care costs. Iron therapy is recommended, usually in combination with an erythropoiesis-stimulating agent (ESA), in many CKD patients with anemia and low iron levels to raise hemoglobin levels to a range of 10 to 12 grams per deciliter; iron deficiency is defined by a ferritin score less than 100 micrograms (mcg) per liter and transferrin saturation (TSAT) less than 20%. OBJECTIVE: To examine the use of intravenous (IV) iron and its associated economic and clinical outcomes in Medicare beneficiaries with stage 3 or stage 4 CKD and anemia. METHODS: This was a retrospective cohort analysis using 2006 and 2007 Medicare 5% Standard Analytic Files (SAF). Use of therapy with IV iron and/or ESAs was identified among patients diagnosed with CKD and anemia. The study index quarter was the first quarter in 2006 during which the patient had primary or secondary diagnoses of both CKD and anemia. Based on the receipt of IV iron or ESA treatment in the index quarter, patients were classified into 1 of 4 treatment groups: IV iron and ESA; IV iron without ESA; ESA without IV iron; neither IV iron nor ESA. Therapy with oral iron was not measurable with this database. Clinical and economic outcomes, including the progression to advanced CKD stages, development of anemia, mortality, hospitalization, and net Medicare reimbursement (i.e., not including patient or supplemental plan contribution) for all-cause health care services, were examined for 1 year following the index quarter. Between-group differences were tested using Pearson chi-square for categorical variables and the Kruskal-Wallis nonparametric test for reimbursement. Multivariate logistic regression models were estimated to assess the associations of mortality, inpatient hospitalization, skilled nursing facility (SNF) admission, and hospice care with treatment regimen, controlling for patient demographic and clinical characteristics. RESULTS: Of the 4,310 study patients with both CKD and anemia, 2,913 (67.6%) received neither IV iron nor ESA; 984 (22.8%) received ESA without IV iron; 277 (6.4%) received IV iron and ESA; and 136 (3.2%) received IV iron without ESA in the index quarter. Logistic regression analyses showed that patients receiving neither IV iron nor ESA (reference group) were at increased risk of death compared with patients receiving both IV iron and ESA (OR = 0.62, 95% CI = 0.42-0.90). Additionally, patients receiving neither IV iron nor ESA were more likely to be hospitalized compared with patients receiving both IV iron and ESA (OR = 0.66, 95% CI = 0.50-0.87), IV iron without ESA (OR = 0.55, 95% CI = 0.38-0.79), and ESA without IV iron (OR = 0.73, 95% CI = 0.62-0.87). Further, patients not receiving IV iron or ESA were more likely to be admitted to an SNF than patients receiving both IV iron and ESA (OR = 0.44, 95% CI = 0.32-0.61), IV iron without ESA (OR = 0.57, 95% CI = 0.36-0.88), and ESA without IV iron (OR = 0.56, 95% CI = 0.47-0.67). Patients receiving neither IV iron nor ESA in the index quarter had the highest mean [SD] total Medicare reimbursement per patient in the subsequent year ($42,353 [$52,887]) compared with patients receiving IV iron without ESA ($28,654 [$32,068]), IV iron and ESA ($34,152 [$30,506]), or ESA without IV iron ($38,172 [$35,591], P = 0.001). CONCLUSIONS: Use rates of IV iron and ESA in a sample of Medicare enrollees with CKD and anemia in 2006 suggest that anemia management therapies may be underutilized; however, oral iron therapy use was not measurable with the study database, and therapies initiated after the index quarter were not measured. Patients not treated with IV iron or ESA had significantly higher rates of hospitalization and SNF admission than patients treated with either IV iron or ESA. Further, mortality was significantly higher in patients receiving neither IV iron nor ESA than in patients who received IV iron and ESA. Additionally, total all-cause health care costs were higher among patients receiving neither IV iron nor ESA treatment compared with patients treated with IV iron and/or ESA.

Frequency and outcomes of blood products transfusion across procedures and clinical conditions warranting inpatient care: an analysis of the 2004 healthcare cost and utilization project nationwide inpatient sample database.

The objective of this retrospective cohort study was to assess frequency and outcomes associated with blood products transfusion. Data from the 2004 Nationwide Inpatient Sample database were used. Length of stay (LOS), postoperative infections, noninfectious transfusion-related complications, in-hospital mortality, and total charges were evaluated for transfused and nontransfused cohorts. Of the estimated 38.66 million discharges in the United States in 2004, 5.8% (2.33 million) were associated with blood products transfusion. Average LOS was 2.5 days longer, and charges were $17 194 higher for the transfused cohort (P < .0001). Odds of death were 1.7 times higher (P < .0001) and odds of infection 1.9 times higher (P < .0001) for the transfused cohort. Increased provider awareness and recognition of the frequency and potential negative outcomes of blood products transfusion may encourage the adoption of novel approaches to minimize intraoperative and early postoperative bleeding, reduce transfusion requirements, and most important, improve patient-level postoperative outcomes and health-related quality of life.