Real-World Outcomes of First-Line Treatment With Anti-PD(L)1-Based Combination Therapy for Nonsquamous Metastatic Non-Small Cell Lung Cancer: A Multiregional Chart Review in Europe, Japan, and the United States.

PURPOSE: Anti-PD-1/PD(L)1-based combination therapy is the standard of care in first line (1L) for metastatic nonsquamous non-small cell lung cancer (mnsqNSCLC) without driver alterations. This study aimed to evaluate real-world clinical outcomes in this population. METHODS: Eligible physicians in the United States, Europe, and Japan abstracted information from medical charts of eligible adult patients with mnsqNSCLC (without EGFR/ALK, no known ROS1 alterations) who initiated 1L anti-PD(L)1-based combination therapy for mnsqNSCLC between 2017 and 2021. Kaplan-Meier analyses were used to assess overall survival (OS), time-to-treatment discontinuation (TTD), and real-world progression-free survival (rwPFS) after 1L initiation. RESULTS: Overall, 142 physicians contributed deidentified data from 430 patients' medical charts. The distribution of PD-L1 expression levels was 31.2% with tumor proportion score (TPS) <1%, 42.3% with TPS 1%-49%, and 26.5% with TPS ≥50%. In 1L, patients received anti-PD(L)1 + chemotherapy (84.6%), anti-PD(L)1 + anti-CTLA4 with or without chemotherapy (11.9%), and anti-PD(L)1 + chemotherapy + anti-vascular endothelial growth factor receptor (3.5%). The median OS was 21.7 months (TPS <1%: 18.3 months; TPS 1%-49%: 21.6 months; TPS ≥50%: 24.0 months). The median TTD was 11.0 months (TPS <1%: 9.1 months; TPS 1%-49%: 10.9 months; TPS ≥50%: 12.2 months). The median rwPFS was 11.2 months (TPS <1%: 9.3 months; TPS 1%-49%: 11.1 months; TPS ≥50%: 13.2 months). CONCLUSION: This study assessed the real-world clinical effectiveness of 1L anti-PD(L)1-based combination therapy for mnsqNSCLC. Results from this study were generally consistent with previous clinical trials and published real-world evidence in 1L mnsqNSCLC.

Clinical and economic burden of medicare beneficiaries with multiple myeloma and renal impairment: An observational study.

Evidence on real-world clinical and economic outcomes in patients with multiple myeloma (MM) and renal impairment (RI) is limited in the United States. This retrospective study aimed to generate an updated comprehensive assessment of the clinical and economic outcomes of MM patients with RI using the Medicare research identifiable files data with Part D linkage, which might assist in assessing the total clinical and socioeconomic burden of these high-risk and challenging-to-treat patients. Treatment patterns and clinical and economic outcomes in first line (1L) to fourth line (4L) therapy were described in Medicare beneficiaries (2012 to 2018) for MM patients with RI (RI MM cohort). For reference purposes, information on a general cohort of MM patients was generated and reported to highlight the clinical and economic burden of RI. Since the goal was to describe the burden of these patients, this study was not designed as a comparison between the 2 cohorts. Compared with the general MM cohort (n = 13,573), RI MM patients (24.9%) presented high MM-associated comorbidities. In the RI MM cohort, bortezomib-dexamethasone (45.7%), bortezomib-lenalidomide (18.6%), lenalidomide (12.3%), and bortezomib-cyclophosphamide (12.1%) were the most prevalent regimens in 1L; carfilzomib and pomalidomide were mostly received in 3L to 4L; and daratumumab in 4L. Across 1L to 4L, the RI MM cohort presented shorter median real-world progression-free survival (1L: 12.9 and 16.4 months) and overall survival (1L: 31.1 and 46.8 months) and higher all-cause healthcare resource utilization (1L incidence rate of inpatient days: 12.1 and 7.8 per person per year) than the general MM cohort. In the RI MM cohort, the mean all-cause total cost increased from 1L to 4L ($14,549-$18,667 per person per month) and was higher than that of the general MM cohort. RI MM patients presented higher clinical and economic burdens across 1L to 4L than the general MM patients in real-world clinical practice.

Real-world clinical outcomes and healthcare costs in patients with Crohn's disease treated with vedolizumab versus ustekinumab in the United States.

OBJECTIVE: To compare real-world treatment persistence, dose escalation, rates of opportunistic or serious infections, and healthcare costs in patients with Crohn's disease (CD) receiving vedolizumab (VDZ) vs ustekinumab (UST) in the United States. METHODS: A retrospective observational study in adults with CD initiated on VDZ or UST on/after 26 September 2016, was performed using the IBM Truven Health MarketScan databases (1 January 2009-30 September 2018). Rates of treatment persistence, dose escalation, opportunistic or serious infection-related encounters, and healthcare costs per patient per month (PPPM) were evaluated. Entropy balancing was used to balance patient characteristics between cohorts. Event rates were assessed using weighted Kaplan-Meier analyses and compared between cohorts using log-rank tests. Healthcare costs were compared between cohorts using weighted 2-part models. RESULTS: 589 VDZ and 599 UST patients were included (172 [29.2%] and 117 [19.5%] were bio-naïve, respectively). After weighting, baseline characteristics were comparable between cohorts. No significant difference in rates of treatment persistence (12-month: VDZ, 76.5%; UST, 82.1%; p = .17), dose escalation (12-month: VDZ, 29.3%; UST, 32.7%; p = .97), or opportunistic or serious infection-related encounters were observed between VDZ and UST. Total mean healthcare costs were significantly lower for patients treated with VDZ vs UST (mean cost difference = -$5051 PPPM; p < .01). Findings were consistent in bio-naïve patients. CONCLUSIONS: In this real-world study, similar treatment persistence, dose escalation, and rates of opportunistic or serious infections were observed with VDZ- and UST-treated patients with CD. However, VDZ was associated with a significantly lower cost outlay for healthcare systems.

Crohn's disease (CD) causes inflammation in the digestive system. Vedolizumab (VDZ) and ustekinumab (UST) are therapies for patients with CD. Little is known about the clinical outcomes and healthcare costs of VDZ versus UST in the real world in the United States. We used health claims data and found that VDZ and UST had comparable real-world clinical outcomes. After 12 months of treatment, the proportions of patients with CD who stayed on treatment and those who needed to increase therapy dose were similar with VDZ and UST. The rate of infection was also similar between the two groups of patients. However, the monthly healthcare costs were $5051 less for patients treated with VDZ than with UST. This was mainly due to the lower cost of VDZ, which was almost half of that of UST. The lower treatment costs with VDZ may provide substantial savings for the healthcare system and patients specifically. Future cost-effectiveness studies on VDZ and UST are needed to aid treatment selection for patients with CD.

Real-World Treatment Patterns and Clinical Outcomes After Platinum-Doublet Chemotherapy and Immunotherapy in Metastatic Non-Small Cell Lung Cancer: A Multiregional Chart Review in the United States, Europe, and Japan.

PURPOSE: To characterize treatment patterns and real-world clinical outcomes of patients with metastatic non-small cell lung cancer (mNSCLC) who developed progression on an anti-PD-1/anti-PD-L1, herein referred to as anti-PD-(L)1, and platinum-doublet chemotherapy. METHODS: Eligible oncologists/pulmonologists in the United States, Europe (France, Germany, and United Kingdom), and Japan completed electronic case report forms for patients with mNSCLC (no evidence of EGFR/ALK/ROS1 alterations). Eligible patients had disease progression on/after an anti-PD-(L)1 and platinum-doublet chemotherapy (received concurrently or sequentially), initiated a subsequent line of therapy (LOT) between 2017 and 2021, and had an Eastern Cooperative Oncology Group (ECOG) performance status 0-2 at this subsequent LOT initiation (index date). Overall survival (OS), time to treatment discontinuation (TTD), and real-world progression-free survival (rwPFS) after index were assessed using Kaplan-Meier analysis. RESULTS: Overall, 160 physicians (academic, 54.4%; community, 45.6%) provided deidentified data from 487 patient charts (United States, 141; Europe, 218; Japan, 128; at mNSCLC diagnosis: median age 66 years, 64.7% male, 81.3% nonsquamous, 86.2% de novo mNSCLC; at line of interest initiation: 86.0% ECOG 0-1, 39.6% liver metastases, 18.9% brain metastases, 79.1% smoking history). The most common treatment regimens upon progression after anti-PD-(L)1/platinum-doublet chemotherapy were nonplatinum chemotherapy (50.5%), nonplatinum chemotherapy plus vascular endothelial growth factor receptor inhibitor (12.9%), and platinum-doublet chemotherapy (6.6%). Median OS was 8.8 months (squamous, 7.8 months; nonsquamous, 9.5 months). Median TTD was 4.3 months (squamous, 4.1 months; nonsquamous, 4.3 months). Median rwPFS was 5.1 months (squamous, 4.6 months; nonsquamous, 5.4 months). CONCLUSION: In this multiregional, real-world analysis of pooled patient chart data, patients with mNSCLC who had disease progression after anti-PD-(L)1/platinum-doublet chemotherapy had poor clinical outcomes with various treatment regimens, demonstrating an unmet clinical need for effective options after failure on anti-PD-(L)1 and platinum-doublet chemotherapy treatments.

Healthcare Resource Utilization and Costs Among Patients With Gastroesophageal Reflux Disease, Barrett's Esophagus, and Barrett's Esophagus-Related Neoplasia in the United States.

Background: Gastroesophageal reflux disease (GERD) is a risk factor for Barrett's esophagus (BE) and BE-related neoplasia (BERN). Objectives: This study aimed to evaluate healthcare resource utilization (HRU) and costs associated with GERD, BE, and BERN in the United States. Methods: Adult patients with GERD, nondysplastic BE (NDBE), and BERN (including indefinite for dysplasia [IND], low-grade dysplasia [LGD], high-grade dysplasia [HGD] or esophageal adenocarcinoma [EAC]), were identified from a large US administrative claims database, the IBM Truven Health MarketScan® databases (Q1/2015-Q4/2019). Patients were categorized into the corresponding mutually exclusive EAC-risk/diagnosis cohorts based on the most advanced stage from GERD to EAC using diagnosis codes in medical claims. Disease-related HRU and costs (2020 USD) were calculated for each cohort. Results: Patients were categorized into the following EAC-risk/diagnosis cohorts: 3 310 385 into GERD, 172 481 into NDBE, 11 516 into IND, 4332 into LGD, 1549 into HGD, and 11 676 into EAC. Disease-related annual mean number of inpatient admissions, office visits, and emergency department visits by cohort were 0.09, 1.45, and 0.19 for GERD; 0.08, 1.55, and 0.10 for NDBE; 0.10, 1.92, and 0.13 for IND; 0.09, 2.05, and 0.10 for LGD; 0.12, 2.16, and 0.14 for HGD; and 1.43, 6.27, and 0.87 for EAC. Disease-related annual mean total healthcare costs by cohort were $6955 for GERD, $8755 for NDBE, $9675 for IND, $12 241 for LGD, $24 239 for HGD, and $146 319 for EAC. Discussion: Patients with GERD, BE, and BERN had important HRU and costs, including inpatient admissions and office visits. As patients progressed to more advanced stages, there was substantially higher disease-related resource utilization, with associated costs being 16 times higher in patients with EAC than those with NDBE. Conclusions: Findings suggest the need for early identification of high-risk individuals prior to progression to EAC to potentially improve clinical and economic outcomes in this population.

Real-world upper endoscopy utilization patterns among patients with gastroesophageal reflux disease, Barrett esophagus, and Barrett esophagus-related esophageal neoplasia in the United States.

This study fills a gap in literature by providing contemporary real-world evidence on the prevalence of patients with gastroesophageal reflux disease (GERD), Barrett esophagus (BE), and Barrett esophagus-related neoplasia (BERN) and their upper endoscopy utilization patterns in the United States. A retrospective cohort study design was used: adults with GERD, nondysplastic Barrett esophagus (NDBE), and BERN (indefinite for dysplasia [IND], low-grade dysplasia [LGD], high-grade dysplasia [HGD], or esophageal adenocarcinoma [EAC]) were identified from the MarketScan databases (January 01, 2015-December 31, 2019). For each disease stage, prevalence of adults in commercial claims by calendar year, annual number of upper endoscopies per patient and time between upper endoscopies were reported. In 2019, in commercial claims (N = 12,363,227), the annual prevalence rate of GERD was 13.7% and 0.70% for BE/BERN, among which, 87.1% had NDBE, 6.8% had IND, 2.3% had LGD, 1.0% had HGD, and 2.8% had EAC. From 2015-2019, the study included 3,310,385 patients with GERD, 172,481 with NDBE, 11,516 with IND, 4332 with LGD, 1549 with HGD, and 11,676 with EAC. Annual mean number of upper endoscopies was 0.20 per patient for GERD, 0.37 per patient for NDBE, 0.43 for IND, 0.58 for LGD, and 0.87 for HGD. Median time (months) to second upper endoscopy was 38.10 for NDBE, 36.63 for IND, 22.63 for LGD, and 11.90 for HGD. Upper endoscopy utilization increased from GERD to BE to BERN, and time between upper endoscopies decreased as the disease stage progressed from BE to BERN, with less frequent utilization in BERN than what would be expected from guideline recommendations for surveillance.

Chronic Myeloid Leukemia: Part II-Cost of Care Among Patients in Advanced Phases or Later Lines of Therapy in Chronic Phase in the United States from a Commercial Perspective.

Background: Tyrosine kinase inhibitors (TKIs) are the standard-of-care treatment for chronic myeloid leukemia in chronic phase (CML-CP). Despite advances in therapy, there remains a proportion of patients with CML-CP that are refractory/intolerant to TKIs, and these patients cycle through multiple lines of therapy. Moreover, even with TKIs, some patients progress to accelerated phase/blast crisis (AP/BC), which is associated with particularly poor clinical outcomes. Objectives: To describe real-world treatment patterns, healthcare resource utilization (HRU), and costs of patients with CML-CP reaching later lines of therapy or progressing to AP/BC in the United States. Methods: Adult CML patients from administrative claims data (January 1, 2000-June 30, 2019) were classified by health state: on third-line (CML-CP On Treatment), on fourth or later lines (CML-CP Post-Discontinuation), or progressed to AP/BC (CML-AP/BC). Outcomes were assessed by health state. Results: There were 296 (4620 patient-months), 83 (1644 patient-months), and 949 (25 593 patient-months) patients classified in the CML-CP On Treatment, CML-CP Post-Discontinuation, and CML-AP/BC cohorts, respectively. Second-generation TKIs (nilotinib, dasatinib, and bosutinib) were most commonly used in the CML-CP On Treatment (69.1% of patient-months) and CML-CP Post-Discontinuation cohorts (59.1% of patient-months). Three-month outpatient incidence rates (IRs) were 7.6, 8.3, and 7.0 visits in the CML-CP On Treatment, CML-CP Post-Discontinuation, and CML-AP/BC cohort, respectively, with mean costs of $597 per service. Three-month inpatient IRs were 0.6, 0.7, and 1.4 days in the CML-CP On Treatment, CML-CP Post-Discontinuation, and CML-AP/BC cohort, respectively, with mean costs of $5892 per day. Mean hematopoietic stem cell transplantation cost was $352 333; mean 3-month terminal care cost was $107 013. Discussion: Cost of CML care is substantial among patients with CML reaching third-line, fourth or later lines, or progressing to AP/BC, suggesting that the disease is associated with a significant economic and clinical burden. From third-line to fourth or later lines, HRU was observed to increase, and the incidence of inpatient days was particularly high for those who progressed to AP/BC. Conclusion: In this study, patients with CML cycling through TKIs in later lines of therapy or progressing to AP/BC experienced substantial HRU and costs, suggesting unmet treatment needs.

Chronic Myeloid Leukemia: Part I-Real-World Treatment Patterns, Healthcare Resource Utilization, and Associated Costs in Later Lines of Therapy in the United States.

Background: Despite advances in tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia in chronic phase (CML-CP), a sizeable proportion of patients with CML-CP remains refractory or intolerant to these agents. Objectives: Treatment patterns, healthcare resource utilization (HRU), and costs were evaluated among patients with CML who received third or later lines of therapy (3L+), a clinical population that has not been previously well-studied, with unmet treatment needs as TKI therapy has repeatedly failed. Methods: Adult patients with CML who received 3L+ were identified in the IBM® MarketScan® Databases (January 1, 2001-June 30, 2019) and the SEER-Medicare-linked database (January 1, 2006-December 31, 2016). Treatment patterns were observed from CML diagnosis. HRU and direct healthcare costs (payer's perspective, 2019 USD) were measured in a 3L+ setting. Results: Among 296 commercially insured patients with 3L+ (median age, 58.5 years; female, 49.7%), the median duration of first-line (1L), second-line (2L), and 3L therapy was 8.5, 4.2, and 8.3 months, respectively. The annual incidence rate during 3L+ was 3.4 for inpatient days, 30.8 for days with outpatient services, and 1.2 for emergency department visits. Mean per-patient-per-month (PPPM) total healthcare costs (pharmacy + medical costs) were $18 784 in 3L+, $15 206 in 3L, and $19 546 in 4L, with inpatient costs driving most of the difference between 3L and 4L (mean [3L] = $2528 PPPM, mean [4L] = $6847 PPPM). Among 53 Medicare-insured patients with 3L+ (median age, 72.0 years; female, 39.6%), the median duration of 1L, 2L, and 3L therapy was 9.7, 5.0, and 7.0 months, respectively. During 3L+, the annual incidence rate was 10.3 for inpatient days, 61.9 for days with outpatient services, and 1.5 for emergency department visits. Mean PPPM total healthcare costs were $14 311 in 3L+, $15 100 in 3L, and $16 062 in 4L. Discussion: Patients with CML receiving 3L+ rapidly cycled through multiple lines. Costs increased from 3L to 4L; in commercially insured patients, inpatient costs were responsible for most of the cost increase between 3L and 4L, underlying these patients' continued need for care. Conclusions: These findings support the need for better treatment options in patients with CML undergoing later lines of therapy.

Tyrosine kinase inhibitor therapy discontinuation in patients with chronic myeloid leukemia in chronic phase in the United States after clinical practice guideline updates.

A physician survey (July 2019-August 2019) and a retrospective patient medical chart review (November 2019-December 2019) were conducted to assess TKI therapy discontinuation practice in patients with Ph + CML-CP in the US after the publication of practice guidelines updated with recommendations for TKI discontinuation. After guideline updates, 90% of physicians from the survey reported attempting TKI discontinuation and 24% of their patients discontinued TKI after achieving an adequate response. Although TKI therapy discontinuation practice is increasing, particularly in community-based practice, a little more than half of physicians were aware of these updated guidelines resulting in TKI discontinuation attempted under suboptimal conditions, mainly limited to first-line TKI therapy, with more than half of physicians without access to at least MR4.5 sensitivity level of detection monitoring. Stricter response criteria per guideline recommendations were observed to relate to lower relapse rates following TKI discontinuation, emphasizing the importance of communicating these recommendations and access to adequate monitoring tools.

Healthcare resource utilization and costs in patients with myelodysplastic syndromes treated with hypomethylating agents: a SEER-Medicare analysis.

AIMS: To describe healthcare resource utilization (HRU) and costs in patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMA) based on HMA-treatment response. MATERIALS AND METHODS: SEER-Medicare data (January 2006-December 2016) were used to identify adults diagnosed with MDS (SEER: January 2009-December 2015) initiated on HMA (index date). HMA-treatment success (indicators: ≥7 HMA cycles, stem cell transplantation, and transfusion independence) or failure (indicators: acute myeloid leukemia [AML], AML-like treatment, and death) was determined using a claim-based algorithm. HRU and costs were assessed from the index date to 1-year post-index, overall and stratified by HMA-treatment success or failure. Among patients with HMA-treatment failure, HRU and costs were also assessed from failure to 1-year post-failure. RESULTS: The study included 3,046 patients (mean age: 77.4 years; females: 36.8%). Rates of HMA-treatment success and failure were 44.4% and 76.2%, respectively (20.6% had HMA-treatment success then failure). Overall, patients had 15.2 inpatient admissions per-100-patients-per-month (median follow-up: 5.9 months). Patients with HMA-treatment success had 7.5 inpatient admissions per-100-patients-per-month (median follow-up: 12.0 months), while those with HMA-treatment failure had 20.4 and 35.3 admissions per-100-patients-per-month pre- and post-HMA-treatment failure, respectively (median follow-up: 4.3 and 1.8 months, pre- and post-HMA-treatment failure, respectively). Mean total healthcare costs were $12,494 per-patient-per-month overall, $8,069 per-patient-per-month among patients with HMA-treatment success, and $13,809 and $19,242 per-patient-per-month pre- and post-HMA-treatment failure, respectively. Outpatient costs (68.3%) were the main contributor of total healthcare costs overall, while inpatient costs (80.3%) were the main cost driver post-HMA-treatment failure. LIMITATIONS: Without available laboratory test results, clinical indicators observed in claims were used to assess HMA-treatment response. CONCLUSIONS: Over 75% of patients with MDS failed HMA-treatment within 6 months of initiation and were observed with more inpatient admissions than those with HMA-treatment success, translating into substantially higher healthcare costs. HMA-treatment failure results in an important economic burden in MDS patients.

Treatment patterns and outcomes in patients with myelodysplastic syndromes treated with hypomethylating agents: a SEER-Medicare analysis.

To describe real-world treatment patterns and outcomes among adult patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMA), patients were identified in the SEER-Medicare database (01/2006-12/2016); 3,046 patients with MDS treated with HMA were included. An algorithm was developed to categorize patients into MDS risk groups: the majority of patients were classified as Higher-risk (70.9%), 8.0% as Intermediate-risk, and 21.1% as Unknown-risk. Overall, 77.4% of patients initiated azacitidine and 22.6% decitabine; they received an average of 5.1 index-HMA cycles, of which 90.9% were complete with a median cycle duration of 28 days. Median survival was 11.6, 18.4, and 19.1 months for the Higher-risk, Intermediate-risk, and Unknown-risk groups, respectively. Median time-to-AML transformation was 19.3 months for the Higher-risk group and 50.4 months for the Intermediate-risk group (not reached for Unknown-risk). Data highlight the unmet medical needs of patients with MDS treated with HMA, particularly for the Higher-risk MDS group.

Characteristics of Patients with Psoriatic Arthritis Receiving Secukinumab and Reasons for Initiation: A US Retrospective Medical Chart Review.

INTRODUCTION: Secukinumab is a fully human anti-interleukin 17A monoclonal antibody approved for the treatment of psoriatic arthritis (PsA) in the United States. Few studies have investigated prescribing patterns among rheumatologists who have initiated secukinumab for the treatment of patients with PsA in real-world settings. This US medical chart review describes clinical and treatment characteristics of patients with psoriatic arthritis (PsA) who were prescribed secukinumab and rheumatologist-reported reasons for prescribing secukinumab in clinical practice. METHODS: This US medical chart review included patients with physician-diagnosed PsA aged ≥ 18 years initiating secukinumab after January 15, 2016. Eligible rheumatologists used online forms to collect patient demographics, disease characteristics, comorbidity profiles, and treatment histories before or on the date of the first secukinumab prescription recorded in the medical chart. Information on reasons for secukinumab prescription and dosing was also collected. RESULTS: Medical charts from 153 patients with PsA who initiated secukinumab were reviewed by 46 rheumatologists between July 7, 2017, and August 11, 2017. Overall, 53.6% of patients were male, mean (standard deviation) age was 47.3 (11.5) years, and 24.8% were biologic naive. The most common reasons for secukinumab prescription among biologic-naive and biologic-experienced patients, respectively, were efficacy/effectiveness of secukinumab (84.2%) and failure of other prior biologics (80.9%). Nearly all patients (94.1%) received a loading regimen, including 150 mg every week (32.7%) and 300 mg every week (61.4%). Overall, 145 patients (94.8%) received ≥ 1 maintenance dose, of whom 49.7% received 150 mg every 4 weeks and 50.3% received 300 mg every 4 weeks. CONCLUSIONS: At the time of the chart review, most patients with PsA who initiated secukinumab were biologic experienced, although one-quarter received secukinumab as first-line biologic therapy. Efficacy/effectiveness of secukinumab and failure of other biologics were the most common reasons for initiating secukinumab. FUNDING: Novartis Pharmaceuticals Corporation, East Hanover, NJ. Plain language summary available for this article.

Tyrosine kinase inhibitor therapy treatment and discontinuation in patients with chronic myeloid leukemia in chronic phase in the United States: a clinical practice perspective.

Tyrosine kinase inhibitor (TKI) therapy discontinuation practice in patients with chronic myeloid leukemia chronic phase (CML-CP) was assessed in real-world practice prior to the release of recommendations on discontinuation. Data were collected from US oncologists/hematologists (through web-based physician survey and patient chart review) on TKI therapy discontinuation practice including monitoring, adequate response for discontinuation, relapse, and symptoms following discontinuation. From the physician survey, 34% of oncologists/hematologists attempted discontinuation, with two-thirds doing so outside of a trial. From the chart review, TKI therapy was discontinued in 3.4% of patients after they achieved an adequate response with the intention to remain CML-therapy-free until disease relapse. Among these patients, 21% relapsed and 17% had symptoms following discontinuation. There was a lack of consensus on the definition of adequate response suggesting that discontinuation was attempted without clear guidelines and under suboptimal conditions underscoring the need for physician education regarding guidelines for TKI therapy discontinuation.

Burden of Infections Among Chronic Myeloid Leukemia Patients Receiving Dasatinib or Nilotinib: A Real-World Retrospective Healthcare Claims Study in the United States.

INTRODUCTION: Tyrosine kinase inhibitors (TKI) have been demonstrated to prolong survival in patients with chronic myeloid leukemia (CML). However, TKIs may be associated with an increased risk of infections. This study compared healthcare resource utilization (HRU) and costs among patients with CML receiving dasatinib or nilotinib, with a focus on infection-related economic outcomes. METHODS: Two large administrative databases were used to identify adult patients newly diagnosed with CML who initiated dasatinib or nilotinib as first- (1L) or second-line (2L) therapy and were classified into the following 1L (dasatinib 1L/nilotinib 1L cohorts) or 2L (dasatinib 2L/nilotinib 2L) cohorts based on the initiated 1L/2L TKI therapy. Infection-related HRU and healthcare costs were compared between cohorts, separately for 1L and 2L. RESULTS: Cohorts included 1156 patients in the dasatinib 1L and 677 patients in the nilotinib 1L cohorts, 322 patients in the dasatinib 2L, and 207 in the nilotinib 2L cohorts. In 1L and 2L, infection-related HRU was higher for dasatinib than nilotinib cohorts. Infection-related inpatient (IP) days constituted a larger proportion of all-cause IP days in the 1L/2L dasatinib than 1L/2L nilotinib cohorts (dasatinib 1L/2L: 53%/58%; nilotinib 1L/2L: 50%/46%). Compared to the nilotinib cohort, the dasatinib cohort had higher all-cause total costs per patient per year by US$17,901 in 1L and $28,625 in 2L. Of the total cost difference, infection-related were $6048 (34%) in 1L and $28,192 (99%) in 2L, largely driven by IP cost differences (1L/2L: 96%/98%). CONCLUSIONS: Dasatinib was associated with higher HRU and healthcare costs compared to nilotinib, particularly related to infections. FUNDING: Novartis Pharmaceutical Corporation.

Treatment patterns, healthcare resource utilization, and costs in patients with acute myeloid leukemia in commercially insured and Medicare populations.

OBJECTIVE: To describe the setting, duration, and costs of induction and consolidation chemotherapy for adults with newly-diagnosed acute myeloid leukemia (AML), who are candidates for standard induction chemotherapy, in the US. METHODS: Adults newly-diagnosed with AML who received standard induction chemotherapy in an inpatient setting were identified from the Truven Health Analytics MarketScan (2006-2015) and SEER-Medicare (2007-2011) databases. Patients were observed from induction therapy start to the first of hematopoietic stem cell transplant, 180 days after induction discharge, health plan enrollment/data availability end, or death. Induction and consolidation chemotherapy were identified using Diagnosis-Related Group codes (chemotherapy with acute leukemia) or procedure codes for AML chemotherapy administration. AML treatment episode setting (inpatient or outpatient), duration, and costs (2015 USD, payers' perspective) were described for commercially insured patients and Medicare beneficiaries. RESULTS: In total, 459 commercially insured patients and 563 Medicare beneficiaries (mean age = 54 and 66 years; 53% and 54% male; respectively) were identified. For induction therapy, mean costs were $145,189 for commercially insured patients and $85,734 for Medicare beneficiaries, and median inpatient duration was 31 days (both). Following induction, 64% of commercially insured patients and 53% of Medicare beneficiaries had ≥1 consolidation cycle; 75% and 65% of consolidation cycles were in an inpatient setting, respectively. For consolidation cycles, in the inpatient setting, mean costs were $28,137 for commercially insured patients and $28,843 for Medicare beneficiaries, median cycle duration was 6 days (both); in the outpatient setting, mean costs were $11,271 for commercially insured patients and $5,803 Medicare beneficiaries, median duration was 5 days (both). LIMITATIONS: Granular information on chemotherapy type administered was unavailable. CONCLUSIONS: This is the first exploratory study providing a complete picture of recent AML treatment patterns and management costs among commercially insured patients and Medicare beneficiaries. There is substantial heterogeneity in the management and costs of AML.

Health Care Resource Utilization and Costs in Patients with Chronic Myeloid Leukemia with Better Adherence to Tyrosine Kinase Inhibitors and Increased Molecular Monitoring Frequency.

BACKGROUND: Frequent molecular monitoring (qPCR tests), as recommended by evidence-based monitoring guidelines, is associated with higher adherence to tyrosine kinase inhibitors (TKIs) in the management of chronic myeloid leukemia (CML); both factors have been associated with better clinical and economic outcomes. OBJECTIVES: To (a) estimate the effect of more frequent qPCR tests on health care resource utilization (HRU) and associated costs, including direct (effect of qPCR test frequency on HRU) and indirect (through TKI adherence) effects, and (b) develop an economic model applicable to multiple clinical practice scenarios. METHODS: Adult patients newly diagnosed with CML who started TKI firstline therapy were identified from U.S. administrative claims data (2010-2015). TKI adherence (medication possession ratio [MPR]), number of inpatient days, emergency room (ER) visits, outpatient service days, and mean costs per HRU event were measured during the first year of CML treatment. Direct and indirect effects of qPCR test frequency were estimated using multivariate regression models. Subsequently, an economic model was developed to assess the overall effect of varying qPCR test frequency on HRU and associated costs during the first year of CML treatment under different clinical practice scenarios; the scenario reported is the increase from 1 to 2 qPCR tests. RESULTS: Of the 1,431 patients included, 36% had no qPCR tests, the average qPCR test frequency was 1.6, and the average MPR was 0.86 during the first year of CML treatment. The direct effect of increasing qPCR test frequency by 1 was associated with 13.0% fewer inpatient days (adjusted incidence rate ratio [adjusted IRR] = 0.87; P = 0.010); 8.3% fewer ER visits (adjusted IRR = 0.92; P = 0.043); and 3.0% more outpatient service days (adjusted IRR = 1.03; P = 0.002). Each increase of 1 test was associated with an increase in TKI adherence by 2.2 percentage points (adjusted MPR difference = 0.022; P < 0.001). When considering the indirect effect of qPCR test frequency through TKI adherence, an increase of 1 qPCR test combined with an increase in TKI adherence by 2.2 percentage points was associated with a greater reduction of inpatient days from 13.0% to 15.2%, ER visits from 8.3% to 8.6%, and a smaller increase of outpatient service days from 3.0% to 2.6%. Based on the economic model, an increase from 1 to 2 qPCR tests, considering the increase in TKI adherence, was associated with a reduction of 0.87 (95% CI = -1.49, -0.18) inpatient days and 0.06 (95% CI = -0.12, 0.05) ER visits, an increase of 0.98 (95% CI = 0.25, 1.60) outpatient service days and a cost savings of $2,918 (95% CI = -5,213, -349) per patient per year. CONCLUSIONS: Closer alignment with the monitoring guidelines' recommended qPCR test frequency and better adherence to TKIs were associated with lower HRU and medical service costs. Managed care initiatives to increase qPCR test frequency and TKI adherence might benefit from an enhanced reduction because of the interaction between both factors. DISCLOSURES: This study was funded by Novartis Pharmaceuticals, which was involved in all stages of the study and in the decision to submit the report for publication. Latremouille-Viau, Guerin, Gagnon-Sanschagrin, and Dea are employees of Analysis Group, which received consulting fees from Novartis Pharmaceuticals for work on this study. Joseph is an employee of Novartis Pharmaceuticals and owns stock in Amgen and Pfizer. Cohen was an employee of Novartis Pharmaceuticals at the time of this study. Portions of this study were presented online (beginning May 20, 2016) as part of the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, on June 3-7, 2016, and as a poster at the American Society of Hematology (ASH) Annual Meeting in San Diego, California, on December 3-6, 2016. Study concept and design were contributed by Latremouille-Viau and Guerin, along with the other authors. Gagnon-Sanschagrin and Dea took the lead in data collection, assisted by the other authors, and data interpretation was performed by Cohen and Joseph, along with the other authors. The manuscript was written by Latremouille-Viau, along with the other authors, and revised by Joseph, along with the other authors.

The economic burden of common adverse events associated with metastatic colorectal cancer treatment in the United States.

AIMS: Adverse events (AEs) associated with treatments for metastatic colorectal cancer (mCRC) may compromise the course of treatment, impact quality-of-life, and increase healthcare resource utilization. This study assessed the direct healthcare costs of common AEs among mCRC patients in the US. METHODS: Adult mCRC patients treated with chemotherapy or targeted therapies were identified from administrative claims databases (2009-2014). Up to the first three mCRC treatment episodes per patient were considered and categorized as with or without the AE system/organ category during the episode. Total healthcare costs (2014 USD) were measured by treatment episode and reported on a monthly basis. Treatment episodes with the AE category were matched by treatment type and line of treatment to those without the AE category. Adjusted total cost differences were estimated by comparing costs during treatment episodes with vs without the AE category using multivariate regression models; p-values were estimated with bootstrap. RESULTS: A total of 4158 patients with ≥1 mCRC treatment episode were included (mean age = 59 years; 58% male; 60% with liver and 14% with lung metastases; 2,261 [54%] with a second and 1,115 [27%] with a third episode). On average, two treatment episodes were observed per patient with an average length of 166 days per episode. Adjusted monthly total cost difference by AE category included hematologic ($1,480), respiratory ($1,253), endocrine/metabolic ($1,213), central nervous system (CNS; $1,136), and cardiovascular ($1,036; all p < .05). LIMITATIONS: Claims do not include information on the cause of AEs, and potentially less severe AEs may not have been reported by the physician when billing the medical service. This study aimed to assess the association between costs and AEs and not the causation of AEs by treatment. CONCLUSIONS: The most costly AEs among mCRC patients were hematologic, followed by respiratory, endocrine/metabolic, CNS, and cardiovascular.

Treatment patterns and healthcare costs among newly-diagnosed patients with chronic myeloid leukemia receiving dasatinib or nilotinib as first-line therapy in the United States.

OBJECTIVE: To compare treatment patterns and economic outcomes of dasatinib and nilotinib as 1st-line therapies for chronic myeloid leukemia (CML). METHODS: Adult CML patients initiated on first-line dasatinib or nilotinib in 2010-2014 were identified from two large US administrative claims databases. Treatment patterns, tyrosine kinase inhibitor (TKI) adherence and healthcare resource utilization (HRU) and costs were measured from the 1st-line TKI initiation (index date) to the end of follow-up. RESULTS: A total of 604 and 418 patients were included in the dasatinib and nilotinib cohorts (mean ages = 50.9 and 52.5 years, 46.4% and 45.7% female), respectively. Among the dasatinib patients, 91% started with 100 mg/day, 3% with <100 mg/day, and 6% with >100 mg/day. Among the nilotinib patients, 76% started with 600 mg/day, 16% with >600 mg/day, and 8% <600 mg/day. The dasatinib cohort had a higher hazard of dose decrease (hazard ratio [HR] = 1.66; p = .002) and of switching to another TKI (HR =1.62; p = .019) compared to the nilotinib cohort. The hazard of dose increase (HR =0.76; p = .423) and treatment discontinuation (HR =1.10; p = .372) were not significantly different between cohorts. There was also no significant difference in TKI adherence levels (mean proportion of days covered [PDC] difference over first 6 months = -0.0003, p = .981; mean PDC difference over first 12 months = -0.0022, p = .880) and HRU (inpatient day incidence rate ratio [IRR] = 1.03, p = .930; emergency room IRR =1.26, p = .197; and days with outpatient services IRR = 1.01, p = .842). The dasatinib cohort incurred higher healthcare costs by $749 per patient per month (p = .044) compared to the nilotinib cohort. LIMITATION: Information on CML phase and Sokal score was not available. CONCLUSIONS: Dasatinib was associated with an increased hazard of dose decrease and switching to another TKI and higher healthcare costs, vs nilotinib.

Treatment patterns, overall survival, healthcare resource use and costs in elderly Medicare beneficiaries with chronic myeloid leukemia using second-generation tyrosine kinase inhibitors as second-line therapy.

Objective Though the median age at diagnosis is 64 years, few studies focus on elderly (≥65 years) patients with chronic myeloid leukemia (CML). This study examines healthcare outcomes among elderly Medicare beneficiaries with CML who started nilotinib or dasatinib after imatinib. Research design and methods Patients were identified in the Medicare Research Identifiable Files (2006-2012) and had continuous Medicare Parts A, B, and D coverage. Main outcome measures Treatment patterns, overall survival (OS), monthly healthcare resource utilization and medical costs were measured from the second-line tyrosine kinase inhibitor (TKI) initiation (index date) to end of Medicare coverage. Results Despite similar adherence, dasatinib patients (N = 379) were more likely to start on the recommended dose (74% vs. 53%; p < 0.001), and to have dose reductions (21% vs. 11%, adjusted hazard ratio [HR] = 1.94; p = 0.002) or dose increases (9% vs. 7%; adjusted HR = 1.81; p = 0.048) than nilotinib patients (N = 280). Fewer nilotinib patients discontinued (59% vs. 67%; adjusted HR = 0.80; p = 0.026) or switched to another TKI (21% vs. 29%; adjusted HR = 0.72; p = 0.044) than dasatinib patients. Nilotinib patients had longer median OS (>4.9 years vs. 4.0 years; p = 0.032) and 37% lower mortality risk than dasatinib patients (adjusted HR = 0.63; p = 0.008). Nilotinib patients had 23% fewer inpatient admissions, 30% fewer emergency room visits, 13% fewer outpatient visits (all p < 0.05), and lower monthly medical costs (by $513, p = 0.024) than dasatinib patients. Limitations Lack of clinical assessment (disease phase and response to first-line therapy) and retrospective nature of study (unobservable potential confounding factors, non-randomized treatment choice). Conclusions In the current study of elderly CML patients, initiation of second-line TKIs frequently occurs at doses lower than the recommended starting doses and, despite this, many patients require dose adjustments. Here, nilotinib patients required fewer dose adjustments than dasatinib patients. Further research focusing on elderly CML patients is warranted in order to help define future best clinical practices.

Comparison of survival and hospitalization rates between Medicare patients with advanced NSCLC treated with bevacizumab-carboplatin-paclitaxel and carboplatin-paclitaxel: a retrospective cohort study.

OBJECTIVE: The use of bevacizumab in advanced non-squamous non-small cell lung cancer (NSCLC) is controversial among elderly patients. This study aimed to compare overall survival for Medicare patients diagnosed with NSCLC and treated with either first-line bevacizumab-carboplatin-paclitaxel (BCP) or carboplatin-paclitaxel (CP). METHODS: Patients ≥ 65 years old, first diagnosed with non-squamous NSCLC stage IIIB/IV between 2006 and 2009, and treated with either first-line BCP or CP, were selected from the SEER-Medicare database that links cancer registry and US Medicare claims data. Kaplan-Meier estimates were used to evaluate survival. Multivariable Cox proportional hazards models were used to compare the effect of BCP versus CP on the hazard of death. Age-stratified analyses were conducted for patients aged 65-74 and ≥ 75 years. RESULTS: Of 1706 patients in the study sample, 592 (34.7%) received BCP and 1114 (65.3%) received CP; 692 (40.6%) were ≥ 75 years. Adjusted median survival time in the BCP versus CP cohorts was 10.5 versus 8.5 months (p = 0.008). The difference in median survival favoring the BCP cohort was statistically significant for both patients aged ≥ 75 years (2.8 months, p = 0.019), and patients aged 65-74 years (1.5 months, p = 0.018). The adjusted hazard of death did not differ between the cohorts (HR: 0.96, 95% CI: 0.86-1.06); however, during the first year of follow-up, when most deaths (>60%) occurred, the hazard of death was 18% lower for the BCP cohort (HR: 0.82, 95% CI: 0.71-0.94). BCP patients also had 18% fewer hospital admissions than CP patients (adjusted incidence rate ratio (IRR): 0.82, 95% CI: 0.72-0.94) and 23% fewer inpatient days (IRR: 0.77, 95% CI: 0.65-0.91). CONCLUSIONS: In this retrospective analysis of Medicare patients in the SEER database, first-line therapy with BCP was associated with longer survival and fewer hospitalizations than CP.