Real-World Effectiveness of Lenvatinib in Hepatocellular Carcinoma Patients with Nonalcoholic Steatohepatitis.

Hepatocellular (HCC) is the most common type of primary liver cancer and the fourth most common cause of cancer-related deaths globally.1 Although most cases of HCC were historically attributed to underlying chronic viral hepatitis, nonalcoholic fatty liver disease is projected to become the most common risk factor for HCC with the rising prevalence of obesity and diabetes mellitus and increasing availability of effective treatments for hepatitis B and C infection.2 Although patients with viral and nonviral HCC seem to have similar overall prognosis,3 prior data have suggested possible differential efficacy of systemic therapies by liver disease etiology. For example, sorafenib was shown to have greater efficacy in patients with chronic hepatitis C infection than other etiologies.4 The aim of our descriptive study was to report the effectiveness of lenvatinib in a real-world cohort of patients with nonalcoholic steatohepatitis (NASH)-related HCC.

Real-world effectiveness of lenvatinib monotherapy among unresectable hepatocellular carcinoma patients in the USA.

Aim: This study evaluated the effectiveness of lenvatinib monotherapy for first-line treatment of unresectable hepatocellular carcinoma (uHCC) in a real-world setting. Materials & methods: This retrospective cohort study included patients who initiated lenvatinib monotherapy as first-line treatment for uHCC (n = 233). Clinical outcomes included provider-reported best response, progression-free survival (PFS) and overall survival (OS). PFS and OS were estimated using Kaplan-Meier methods. Results: Most patients (67.8%) were male. A total of 44.6% had Child-Pugh A and 39.1% had Child-Pugh B. Dose reductions were reported in 9%. Median PFS and OS were not reached. At 6 and 12 months, landmark PFS were 85.1 and 64.9%, respectively; landmark OS were 91.8 and 72.6%, respectively. Conclusion: These results affirm the clinical effectiveness of first-line lenvatinib monotherapy in uHCC.

Lay abstract Lenvatinib is a targeted therapy that prevents tumor growth. It was approved for the treatment of advanced liver cancer in 2018, but few studies have examined how it is used in everyday clinical practice, especially in the USA. In this study, we reviewed the medical records of 233 patients in the USA with unresectable hepatocellular carcinoma, who were treated with lenvatinib in first line to better understand its effectiveness and use in real-world care. We collected information on how long they were on treatment and time to tumor progression and/or death. Overall, our study found that in this demographically and clinically diverse sample, results affirm findings from prior studies that found lenvatinib is an effective treatment for patients with unresectable hepatocellular carcinoma.

Long-Term Pain Management and Health Care Resource Use Among an Employed Population in Japan with Knee Osteoarthritis Combined with Low Back Pain.

OBJECTIVE: Assess long-term comorbidity burden and pain management patterns among working-age patients with knee osteoarthritis (KOA) only without low back pain (LBP) (KOA-noLBP) and patients with KOA plus LBP (KOA+LBP) in Japan. METHODS: Retrospective claims data analyses were conducted on data from the Japan Medical Data Center (JMDC) database. Adult patients (≥40 years) with a diagnosis of knee osteoarthritis (KOA) (January 1, 2011-December 31, 2012) and 5 years of follow-up were evaluated. The first claim with a KOA diagnosis defined the index date. Longitudinal pain management patterns were assessed in both cohorts. RESULTS: Overall, 1,828 patients met study criteria (717 with KOA-noLBP; 1,111 with KOA+LBP). The mean age of patients with KOA-noLBP was 52.1 years, and that of patients with KOA+LBP was 53.1 years, with more females in the KOA+LBP cohort (49.4% vs. 55.0%). Regardless of cohort, >90% of patients received pharmacological intervention during the 5-year follow-up period. The most common regimen first received was either topical or oral nonsteroidal anti-inflammatory drugs. A higher mean number of pharmaceutical treatments were received by patients in the KOA+LBP cohort (3.6) than by patients in the KOA-noLBP cohort (2.7) during the follow-up period. Regardless of cohort, most of the direct medical cost was derived from medication. CONCLUSION: This study demonstrates that a greater proportion of the JMDC population of working individuals with KOA were comorbid with LBP and received pain-related treatment in the long-term perspective relative to patients with KOA without LBP. Appropriate pain management for both KOA and LBP would be key for effective resource utilization in an aging society facing socioeconomic burdens.

Treatment Patterns, Statin Intolerance, and Subsequent Cardiovascular Events Among Japanese Patients With High Cardiovascular Risk Initiating Statin Therapy.

BACKGROUND: This study examined treatment patterns, possible statin intolerance, and incidence of cardiovascular events (CVEs) in 2 cohorts of patients with high cardiovascular risk (i.e., patients with atherosclerotic cardiovascular disease [ASCVD] and patients with diabetes mellitus).Methods and Results:A retrospective cohort study examined adults initiating either a statin or ezetimibe from 1 January 2006 to 31 May 2014 in the Japan Medical Data Center database. The first observed statin or ezetimibe prescription defined the index date. Patients had ≥12 months of pre- and post-index date plan enrollment. Two high-risk cohorts, the ASCVD cohort and diabetes cohort, were created based on diagnoses observed during the 12 months' pre-index date. Treatment patterns, possible statin intolerance, and incidence of CVEs were reported. In the ASCVD cohort (n=5,302), 32.9% discontinued therapy, 7.7% switched to a non-index statin or non-statin lipid-lowering therapy, and 11.2% augmented index therapy in the 12 months' post-index date; only 0.3% were using high-intensity statins and 10% had possible statin intolerance. Also, 8.1% had any new CVE during the follow-up period. Treatment patterns and incidence of CVEs among the diabetes cohort were similar to those of the ASCVD cohort. CONCLUSIONS: High cardiovascular risk Japanese patients had frequent treatment modifications, although use of high-intensity statin doses was rare. These patterns may indicate that alternative therapies for lipid lowering are needed.

Real-World Treatment Patterns and Clinical Outcomes Among Patients With Advanced Renal Cell Carcinoma.

BACKGROUND: Nearly 30% of new renal cell carcinoma (RCC) cases are diagnosed at an advanced or metastatic stage. Recent approvals of immunotherapies (IO) have significantly impacted patient care, but real-world outcomes of these treatments have not been widely evaluated. METHODS: Eligible physicians abstracted demographic and clinical data from patient medical records for patients with advanced clear and non-clear cell RCC (aRCC) who initiated treatment between January 1, 2018, and December 31, 2020. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. A multivariate Cox regression model was developed to assess the impact of treatment category on clinical outcomes while controlling for International Metastatic RCC Database Consortium (IMDC) risk category, histology, and other patient characteristics. RESULTS: A total of 498 patients were included (201 from US, 62 from Canada, 58 from UK, 59 from France, 58 from Germany, 60 from Spain). Of these, 250 received tyrosine kinase inhibitor (TKI) monotherapy, 197 received immunotherapy (IO) combination (119 IO+TKI, 78 IO+IO), and 32 received IO monotherapy as first-line treatment for aRCC; 19 patients received various other regimens. 16% of patients had a favorable IMDC risk score. Based on results of multivariable Cox regression, PFS (hazard ratio [HR] [95% confidence interval (CI)]: 0.50 [0.36-0.72]) (P < .001) and time to next treatment (TTNT) were significantly longer (HR [95% CI]: 0.54 [0.39-0.73]) (P < .001) for patients treated with IO combination versus TKI monotherapy. IO combination had a numerically reduced, but statistically insignificant, risk of death versus TKI monotherapy (HR: 0.66; P = .114). IO+TKI combination was associated with significantly longer PFS and reduced risk of progression (HR: 0.52; P = .04) versus IO+IO combination; similar results were observed for TTNT (HR: 0.57; P = .03). CONCLUSION: Our evaluation of real-world treatment outcomes in aRCC revealed that IO + TKI combination is associated with improved PFS and prolonged TTNT compared with TKI monotherapy and IO+IO combination.

Real-world effectiveness of lenvatinib monotherapy in previously treated unresectable hepatocellular carcinoma in US clinical practice.

BACKGROUND: Lenvatinib monotherapy was approved in the United States for first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC) in 2018. This study assessed real-world treatment patterns and outcomes of lenvatinib beyond first-line systemic treatment in the United States. METHODS: A retrospective study was conducted among US adults (≥18 years) with uHCC. Eligible patients initiated lenvatinib monotherapy as second- or later-line systemic therapy (2L-plus) from August 2018 to September 2019. Clinical outcomes included physician-reported best response, progression-free survival (PFS), and overall survival (OS). RESULTS: Of 164 patients who received lenvatinib in 2L-plus, most (n = 133; 81.1%) received lenvatinib in 2 L. There were 109 patients (66.4%) who initiated lenvatinib after immunotherapy. At lenvatinib initiation, only 31.1% of patients had Child-Pugh class A, while half (49.4%) had Child-Pugh class B. Most patients had Barcelona Clinic Liver Cancer stage B (23.8%) or C (38.4%) uHCC. Median duration of lenvatinib treatment was 6.9 months, with 42.7% of patients still on treatment at the end of follow-up. Physician-reported best response was complete and partial response for 8.5% and 44.5% of patients, respectively. PFS and OS rate estimates from lenvatinib initiation at 12 months were 51.7% and 57.8%, respectively. Among patients treated after immunotherapy, complete and partial responses were 10.1% and 43.1%, respectively, and PFS and OS estimates from lenvatinib initiation at 12 months were 52.8% and 60.0%, respectively. CONCLUSION: This retrospective study suggests clinical effectiveness of lenvatinib monotherapy in a real-world setting among previously treated patients with uHCC, including among those previously treated with immunotherapy.

Observational study of the outcomes and costs of initiating maintenance therapies in patients with moderate exacerbations of COPD.

BACKGROUND: There are limited data describing patients with moderate COPD exacerbations and evaluating comparative effectiveness of maintenance treatments in this patient population. The study examined COPD patients with moderate COPD exacerbations. COPD-related outcomes were compared between patients initiating fluticasone propionate-salmeterol 250/50 mcg (FSC) vs anticholinergics (ACs) following a moderate COPD exacerbation. METHODS: This retrospective observational study used a large administrative claims database (study period: 2003-2009) to identify and describe patients with an initial, moderate COPD exacerbation. A descriptive analysis of patients with moderate COPD exacerbations was done evaluating maintenance treatment rates, subsequent COPD exacerbation rates, and COPD-related costs during a 1-year period. A cohort analysis compared COPD exacerbation rates and associated costs during a variable-length follow-up period between patients initiating maintenance therapy with FSC or ACs. COPD exacerbations were reported as rate per 100 patient-years, and monthly costs were reported (standardized to USD 2009). COPD exacerbation rates between cohorts were evaluated using Cox proportional hazards models, and costs were analyzed using generalized linear models with log-link and gamma distribution. RESULTS: 21,524 patients with a moderate COPD exacerbation were identified. Only 25% initiated maintenance therapy, and 13% had a subsequent exacerbation. Annual costs averaged $594 per patient. A total of 2,849 treated patients (FSC = 925; AC = 1,924) were eligible for the cohort analysis. The FSC cohort had a significantly lower rate of COPD exacerbations compared to the AC cohort (20.8 vs 32.8; P = 0.04). After adjusting for differences in baseline covariates, the FSC cohort had a 42% significantly lower risk of a COPD exacerbation (HR = 0.58; 95% CI: 0.38, 0.91). The FSC cohort incurred significantly higher adjusted pharmacy costs per patient per month by $37 (95% CI: $19, $72) for COPD-related medications vs the AC cohort. However, this increase was offset by a significant reduction in adjusted monthly medical costs per patient for the FSC vs the AC cohort ($82 vs $112; P < 0.05). Total monthly COPD-related costs, as a result, did not differ between cohorts. CONCLUSIONS: Only a quarter of patients with a moderate COPD exacerbation were subsequently treated with maintenance therapy. Initiation of FSC among those treated was associated with better clinical and economic outcomes compared to AC.

Herpes Zoster Incidence and Burden in Adults With Type 2 Diabetes in the U.S.: A Retrospective Database Analysis.

OBJECTIVE: Data on the real-world burden of herpes zoster (HZ) in adults with type 2 diabetes (T2D) in the U.S. are limited. We assessed HZ in patients with and without T2D and measured the impact of HZ on health care resource use (HCRU) and costs. RESEARCH DESIGN AND METHODS: This retrospective cohort analysis used U.S. commercial claims data (sourced from claims incurred between 1 January 2012 and 31 July 2018). HZ incidence rates/1,000 person-years (PYs) were calculated in patients with and without T2D. HZ risk was evaluated using Poisson regression to generate adjusted incidence rate ratios (aIRRs). Patients with T2D with HZ were propensity score matched to patients with T2D only and to patients with HZ without T2D. HCRU and costs were compared across cohorts during a 1-year follow-up period. Cox proportional hazards analyses evaluated factors associated with HZ-related complications. RESULTS: Crude HZ incidence rates in patients with and without T2D were 9.8/1,000 PY and 2.6/1,000 PY, respectively. T2D patients were almost twice as likely to be diagnosed with HZ (aIRR 1.84; 95% CI 1.82-1.85). HZ was associated with increased HCRU and health care costs. At 12 months, unadjusted incremental all-cause health care costs for patients with T2D with HZ versus patients with T2D without HZ were $5,216. The unadjusted incremental HZ-related health care costs for patients with T2D with HZ versus patients with HZ without T2D were $2,726. Age was the most important predictor for HZ-related complications. CONCLUSIONS: Given the increased risk of HZ and HCRU and cost burden in patients with T2D, HZ prevention in patients with T2D may be beneficial.

Overall survival, adverse events, and economic burden in patients with chronic lymphocytic leukemia receiving systemic therapy: Real-world evidence from the medicare population.

BACKGROUND: Information on overall survival (OS) and adverse events (AEs) in patients with chronic lymphocytic leukemia (CLL) is mostly available from clinical trials. We therefore conducted a population-based retrospective cohort study to assess OS, incidence of AEs, and economic burden in real-world practice among Medicare patients treated for CLL. METHODS: Patients with CLL receiving ≥1 systemic therapy from 2013 to 2015 were selected from the Medicare claims database and followed from the start of first observed systemic therapy (index date) through December 2016 or death. OS for patients receiving each of the most commonly observed treatments was estimated by the Kaplan-Meier method. AEs were assessed among patients receiving these treatments across all observed lines of therapy. All-cause direct medical costs were assessed from the Medicare system perspective. RESULTS: Among 7,965 eligible patients across all observed therapy lines, ibrutinib monotherapy (Ibr; n = 2,708), chlorambucil monotherapy (Clb; n = 1,620), and bendamustine/rituximab (BR; n = 1,485) were the most common treatments. For first observed therapy, 24-month OS estimates for Ibr, Clb, and BR recipients were 69% (95% CI = 68%-71%), 68% (95% CI = 65%-71%), and 79% (95% CI = 77%-81%) respectively. The most frequently recorded AEs in patients receiving these treatments in any observed line of therapy were neutropenia, hypertension, anemia, and infection. For all patients, the mean monthly all-cause cost during the follow-up period was $8,974 (SD = $11,562); cost increased by the number of AEs, from $5,144 (SD = $5,409) among those with 1-2 AEs to $10,077 (SD = $12,542) among those with ≥6 AEs. CONCLUSION: Over two-thirds of patients survived at least 2 years after starting their first observed therapy for CLL. Our findings highlight considerable susceptibility to AEs and unmet medical need in Medicare patients with CLL treated in routine practice. Medicare incurred substantial economic burden following initiation of systemic therapy, and patients with greater numbers of AEs accounted disproportionately for the high overall cost of CLL management.

European and US Real-World Treatment Patterns in Patients with Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer: A Retrospective Medical Record Review.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line (1L) therapy for EGFR mutation-positive (EGFRm) advanced/metastatic non-small cell lung cancer (NSCLC). OBJECTIVE: Our objective was to describe real-world treatment patterns and T790M testing practices in patients with 1L disease progression (Europe/USA) following treatment with first- or second-generation EGFR-TKIs. METHODS: This was a retrospective, non-interventional medical record review of patients with EGFRm locally advanced/metastatic NSCLC from routine clinical practice (EGFR-TKI initiation: 1 January 2015 to 31 December 2017; follow-up: last available medical record). Endpoints were demographic/clinical characteristics, incidence of central nervous system (CNS) metastases/leptomeningeal disease, second-line (2L) treatment, T790M mutation testing, and osimertinib treatment prevalence. RESULTS: Among 469 patients, 73% (n = 341/469) progressed on 1L EGFR-TKI treatment. Of those who progressed, 74% (n = 252/341) were tested for T790M, with 50% (n = 126/252) testing positive; 75% (n = 94/126) of T790M-positive patients received osimertinib (mostly 2L). Of the patients with progression, 24% (n = 83/341) did not receive 2L treatment, and 88% (n = 73/83) of these patients died. At diagnosis of advanced disease, 9% of patients (n = 41) had CNS metastases; at EGFR-TKI initiation, 14% of patients (n = 68) had CNS metastases. Over the study period, 11% of patients (n = 42) developed CNS metastases not detected at NSCLC diagnosis. CONCLUSIONS: Rates of resistance mutation testing and subsequent utilization of recommended 2L therapies could be improved. As more targeted therapies are developed, it will be crucial to improve the molecular testing rates to ensure patients receive appropriate, effective, and timely treatment.

Real-world evidence on survival, adverse events, and health care burden in Medicare patients with mantle cell lymphoma.

Most data on overall survival (OS) and adverse events (AEs) in patients with mantle cell lymphoma (MCL) are from controlled trials; therefore, in this population-based study, we retrospectively assessed treatment patterns, OS, and AEs in MCL patients initiating systemic treatment during 2013-2015 using the United States Medicare claims database. Among 1390 eligible patients (median age = 74 years), chemoimmunotherapy with bendamustine/rituximab (BR) was the preferred choice in first-line (35.3%), followed by ibrutinib (33.5%), rituximab (9.1%), and rituximab/cyclophosphamide/doxorubicin/vincristine (R-CHOP) (6.8%). Twenty-four-month OS was 73% for BR; 47%, ibrutinib; 72%, rituximab; and 71%, R-CHOP. For the four most commonly used regimens, neutropenia, anemia, hypertension, and infection were the most frequent AEs. Patients with ≥3 AEs had nearly four times higher monthly costs than those with 0-2 AEs in the first observed therapy line. Findings demonstrate a substantial increase in the economic burden as the number of AEs increased among the Medicare MCL patients.

Treatment patterns, adverse events, and direct and indirect economic burden in a privately insured population of patients with HR+/HER2- metastatic breast cancer in the United States.

BACKGROUND: Real-world evidence specific to HR+/HER2- metastatic breast cancer (MBC) prior to introduction of CDK4/6 inhibitors is limited. In an effort to provide context for the introduction of new treatments, we assessed treatment patterns, adverse events, productivity loss, and direct/indirect economic burden in a privately insured population of patients with HR+/HER2- MBC. RESEARCH DESIGN AND METHODS: Using a retrospective cohort design, patients aged 18-64 years, selected from MarketScan databases (2007-2014), were analyzed using descriptive and multivariable methods. RESULTS: Among 5,563 eligible patients, endocrine therapy was the most common first-line (1L) therapy; its utilization trended downward from 63% (1L) to 23% (4L), with a simultaneous increase in chemotherapy use, 25% (1L) to 50% (4L). Two hundred and seventy-eight unique treatment regimens were used in the 1L setting. The average per patient monthly all-cause costs were $14,424. The 12-month indirect costs for short-term disability were substantially higher in MBC patients ($10,397) than in matched noncancer patients ($394). CONCLUSION: The increasing use of chemotherapy as patients progressed to second and later lines and the substantial direct/indirect economic burden underscore an unmet need. The high number of 1L regimens highlights significant heterogeneity and a lack of consensus related to the management of HR+/HER2- MBC in routine practice.

Longitudinal Assessment of Pain Management Among the Employed Japanese Population with Knee Osteoarthritis.

PURPOSE: To assess comorbidity burden and pain-management patterns among working-aged patients with knee osteoarthritis only (KOA/O) and patients with knee osteoarthritis plus osteoarthritis at another site (KOA/+) in Japan. PATIENTS AND METHODS: Retrospective claims data analysis was conducted using the Japan Medical Data Center database. Working-aged adults (aged 40 to 71 years) with 5 years of follow-up and diagnosed with knee osteoarthritis (KOA) between January 1, 2011, and December 31, 2012, were evaluated. The first claim with a KOA diagnosis defined the index date. Patients were divided into two mutually exclusive cohorts: KOA/O and KOA/+. Longitudinal pain-management patterns during each year of follow-up were analyzed. RESULTS: A total of 2542 patients met study criteria: 1575 KOA/O and 967 KOA/+. Mean age and number of comorbidities were higher among the KOA/+ versus KOA/O cohort. Pharmaceutical treatment was received by 91.5% of patients in the KOA/+ compared with 85.1% of patients in the KOA/O cohort during the first year of follow-up. The most common pharmacological treatment received during the first year of follow-up was either topical or oral nonsteroidal anti-inflammatory drugs for both cohorts. During each year of follow-up, the KOA/+ cohort had greater proportion of patients with at least one health-care encounter (ie, hospital admissions, outpatient and pharmacy visits) and higher direct medical costs compared with the KOA/O cohort. CONCLUSION: This study demonstrates that a greater proportion of the working population with KOA/+ received pain-related treatment compared with patients with KOA/O. Further studies are necessary to evaluate appropriate pain management for both KOA only and KOA with other sites.

Real-World Treatment Patterns, Outcomes, and Healthcare Resource Utilization in Relapsed or Refractory Multiple Myeloma: Evidence from a Medical Record Review in France.

BACKGROUND: Limited data are available from real-world practices in Europe describing prevailing treatment patterns and outcomes in relapsed/refractory multiple myeloma (RRMM), particularly by cytogenetic risk. METHODS: A retrospective medical record review was conducted in 200 RRMM patients in France. From first relapse, patients were assessed on second-/third-line treatments, progression-free survival (PFS), overall survival (OS), and healthcare utilization. RESULTS: Fifty-five high risk and 113 standard risk patients were identified. Overall, 192 patients (96%) received second-line therapy after relapse. Lenalidomide-based regimens were most common (>50%) in second line. Hospitalization incidence in high risk patients was approximately twice that of standard risk patients. From Kaplan-Meier estimation, median (95% CI) second-line PFS was 21.4 (17.5, 25.0) months (by high versus standard risk: 10.6 [6.4, 17.0] versus 28.7 [22.1, 37.3] months). Among second-line recipients, 47.4% were deceased at data collection. Median second-line OS was 59.4 (38.8, NE) months (by high versus standard risk: 36.5 [17.4, 50.6] versus 73.6 [66.5, NE] months). CONCLUSIONS: The prognostic importance of cytogenetic risk in RRMM was apparent, whereby high (versus standard) risk patients had decidedly shorter PFS and OS. Frequent hospitalizations indicated potentially high costs associated with RRMM, particularly for high risk patients. These findings may inform economic evaluations of RRMM therapies.

Adverse events, resource use, and economic burden associated with mantle cell lymphoma: a real-world assessment of privately insured patients in the United States.

In view of recent therapeutic advances in mantle cell lymphoma (MCL), the aim of this retrospective cohort analysis was to assess treatment patterns, adverse events (AEs), resource utilization, and health care costs in patients with MCL in a US-based commercial claims database. A total of 783 patients with MCL (median age = 65 years) were selected. Among patients receiving systemic therapy (n = 457), the most common treatment regimens were bendamustine/rituximab (BR) (41.1%), rituximab/cyclophosphamide/doxorubicin/vincristine (RCHOP) (26.7%), rituximab monotherapy (20.4%), and ibrutinib monotherapy (14.2%). Mean monthly costs during treatments with BR, RCHOP, rituximab, and ibrutinib were $12,958, $24,719, $13,153, and $21,690, respectively. Mean monthly cost during follow-up was $13,650 among patients with ≥6 AEs versus $5131 among those without AEs. The costs of MCL varied considerably by treatment regimen and care setting. The overall economic burden of managing patients with MCL can be substantially affected by costs associated with managing AEs occurring during treatment.

Treatment Patterns and Outcomes Associated With Palbociclib Plus Letrozole for Postmenopausal Women With HR+/HER2- Advanced Breast Cancer Enrolled in an Expanded Access Program.

PURPOSE: To evaluate treatment patterns and clinical outcomes of patients who received palbociclib in combination with letrozole in any line of therapy for treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer in an expanded access program (EAP) in the United States. PATIENTS AND METHODS: A retrospective chart review study was conducted of patients previously enrolled in the palbociclib EAP. Complete data from time of initial diagnosis of metastatic breast cancer until date of chart abstraction were obtained. Clinical outcomes as assessed by site investigators included clinical benefit rate, progression-free survival, and overall survival. Survival was descriptively assessed using Kaplan-Meier methods. RESULTS: Of 238 patients enrolled in the EAP, data from 126 patients were included. Median age was 62.5 years at EAP enrollment; 25% had de novo metastatic disease. Visceral disease was present in 71% of patients. The disease of most patients was heavily pretreated; nearly 60% of patients had received 3 or more prior lines for metastatic disease before initiating palbociclib + letrozole therapy. Most patients (87%) had received prior endocrine therapy, and 68% had received prior chemotherapy for metastatic disease. Patients with prior endocrine therapy for metastatic disease had a clinical benefit rate of 30%, while those with prior chemotherapy had a 26% clinical benefit rate. Patients receiving 2 or more prior lines had 6- and 12-month progression-free survival rates of 35% and 21%, respectively, and 12- and 24-month overall survival rates of 62% and 35%, respectively. CONCLUSION: Most patients derived benefit from palbociclib + letrozole treatment despite having received multiple prior treatment lines for metastatic disease.

Treatment patterns, adverse events, and economic burden in a privately insured population of patients with chronic lymphocytic leukemia in the United States.

INTRODUCTION: Contemporary data describing treatment patterns, adverse events (AEs), and outcomes in patients with chronic lymphocytic leukemia (CLL) in clinical practice are lacking. We conducted a retrospective cohort study and assessed treatment patterns, AEs, health-care resource use (HCRU), and costs in patients with diagnosis of CLL. METHODS: Using a nationally representative population of privately insured patients in the US, adult patients with CLL diagnosis (July 2012-June 2015) were selected if they had continuous health plan enrollment for ≥12 months before the first CLL diagnosis without any evidence of any CLL-directed treatment. Treatment patterns up to four lines of therapy (LOT) and occurrence of AEs during CLL therapies were assessed. Mean per-patient monthly HCRU and costs were assessed overall and by number of unique AEs. RESULTS: Of all patients meeting the selection criteria (n = 7,639; median age, 66 years), 18% (n = 1,379) received a systemic therapy during study follow-up. Of these, bendamustine/rituximab (BR) was the most common first observed regimen (28.1%), while ibrutinib was the most common therapy in the second (20.8%) and third (25.5%) observed regimens. The mean monthly all-cause and CLL-related costs, among patients treated with a systemic therapy, were $7,943 (SD = $15,757) and $5,185 (SD = $9,935), respectively. Mean monthly all-cause costs increased by the number of AEs (from $905 [SD = $1,865] among those with no AEs to $6,032 [SD = $13,290] among those with ≥6 AEs). CONCLUSIONS: Chemoimmunotherapy, particularly BR, was the most common first observed therapy for CLL, whereas ibrutinib was most preferred in the second and third observed lines of therapy during the study period. Findings demonstrate that the economic burden of AEs in CLL is substantial.

Treatment patterns, survival and economic outcomes in Medicare-enrolled, older patients with HR+/HER2- metastatic breast cancer.

Background: Endocrine therapy (ET) remains a foundation of systemic therapy for HR+/ HER2- metastatic breast cancer (MBC), although chemotherapy (CT) is used in select patients. In this "real-world" study, we explored treatment patterns, health care resource use (HCRU), costs, adverse events (AEs) and overall survival (OS) in Medicare-enrolled, older patients with HR+/HER2- MBC. Methods: Patients with HR+/HER2- MBC (2007-2011) and aged >66 years were retrospectively analyzed using the SEER-Medicare data. Treatment patterns, HCRU, costs, AEs and OS after MBC diagnosis through end of study period (31 December 2013) were examined using descriptive and multivariable analyses. Results: Among 3622 eligible patients, ET was the most common treatment (77%), followed by CT (50%), radiation (48%) and surgery (19%). The proportion of patients treated with ET monotherapy decreased across therapy lines, from 74% in first line (1 L) to 35% in 4 L. The total number of unique therapy regimens used was 181 in 1 L, 171 in 2 L, 128 in 3 L, and 95 in 4 L. The median OS from MBC diagnosis was 25.3 months (95% CI, 24.0-26.7). In multivariable analyses, receipt of CT and combination CT + ET (versus ET monotherapy) in 1 L, metastatic disease at initial diagnosis, larger tumor size, and presence of visceral and brain metastases at MBC diagnosis significantly predicted receipt of 2 L therapy. Conclusions: ET was the most common first-line treatment for study patients, but its use decreased gradually in the subsequent lines. The heterogeneity in the treatment selection highlights a lack of consensus for the management of HR+/HER2- MBC in routine practice.

Medical record review of transition to lanreotide following octreotide for neuroendocrine tumors.

BACKGROUND: Octreotide has been used for decades in the United States (US) and Europe to treat patients with advanced neuroendocrine tumors (NETs). Lanreotide was approved in 2014 to improve progression-free survival (PFS) in patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic NETs. Therefore, clinicians and patients may consider sequencing therapy from octreotide to lanreotide. However, current real-world outcomes data on patients who have made this transition is limited. METHODS: We conducted a multicenter, noninterventional, retrospective medical record review of patients with locally advanced or metastatic gastroenteropancreatic NETs (NCT03112694). Included patients had been treated with long-acting octreotide monotherapy for ≥90 days before transitioning to lanreotide monotherapy and continued on lanreotide for ≥90 days. Abstractors entered patient demographic and clinical data into a customized, web-based case report form. We assessed clinically defined PFS and other tumor-related outcomes while patients were treated with lanreotide. Outcomes were analyzed according to level of response at the time of transition from octreotide to lanreotide: progressive disease, nonprogressive disease, or unknown. Statistical analyses were descriptive. Clinically defined PFS and duration of treatment with lanreotide were estimated using the Kaplan-Meier method. RESULTS: Data were abstracted for 91 patients with gastroenteropancreatic NETs who received long-acting octreotide followed by lanreotide at six US based sites. At initial diagnosis, 71.4% of patients had stage IV disease. Small intestine (63.7%) and pancreas (14.3%) were the most common primary tumor sites. Mean [standard deviation (SD)] duration of follow-up from diagnosis was 70.6 (41.3) months. Patients received long-acting octreotide for a mean (SD) of 38.4 (32.8) months. When patients transitioned to lanreotide, 57.1% had nonprogressive disease on octreotide, 30.8% had progressive disease, and the remainder had unknown disease status. The most common reasons for switching from octreotide to lanreotide were progressive disease (22.0%), formulary change (15.4%), and patient preference (9.9%). Patients received lanreotide for a median (95% CI) duration of 24.7 (16.7-59.9) months. At the end of follow-up, 74% of patients remained on lanreotide monotherapy. Progression occurred in 24.2% of patients during lanreotide treatment. Overall median (95% CI) clinician-defined PFS following the transition to lanreotide was estimated to be 23.7 months [20.2 months-NE (not estimable)]. Patients with nonprogressive disease when they transitioned to lanreotide experienced a median clinician-defined PFS of 24.7 (17.0-NE) months. Among patients reported to have progressive disease when they transitioned to lanreotide, median (95% CI) clinician-defined PFS was estimated to be 15.2 (11.4-NE) months. There were no material differences in adverse events recorded during the long-acting octreotide and lanreotide treatment periods. CONCLUSIONS: Our study suggests that lanreotide monotherapy is well tolerated and may contribute to stabilization of disease in a subset of patients with locally advanced or metastatic gastroenteropancreatic NETs previously treated with long-acting octreotide.

Treatment patterns, health care resource utilization, and costs in Japanese adults with attention-deficit hyperactivity disorder treated with atomoxetine.

OBJECTIVE: To describe the characteristics and medication treatment patterns of adult patients with attention-deficit/hyperactivity disorder (ADHD) prescribed atomoxetine in Japan. MATERIALS AND METHODS: A retrospective analysis of insurance claims data was conducted using the Japan Medical Data Center database. Adults (≥18 years) with ADHD who had ≥1 atomoxetine claim from January 1, 2013 to December 31, 2014, and ≥180 to ≤900 days of follow-up were included. First atomoxetine claim defined the index date. Patient characteristics included age, gender, and comorbid conditions. Treatment patterns assessed included rates of atomoxetine discontinuation, switching, persistence, adherence (assessed via the medication possession ratio), and use of concomitant medications. RESULTS: A total of 457 adults met all the inclusion criteria. Mean (SD) age was 32.7 (10.4) years, and 61.0% of patients were male. Nearly 72.0% of the patients had at least one comorbid mental health condition in the baseline period; depression (43.8%) and insomnia (40.7%) were the most common mental health comorbidities. Most common physical comorbidities were chronic obstructive pulmonary disease (14.4%) and diabetes (12.9%). Non-ADHD-specific psychotropics were prescribed to 59.7% of patients during the baseline period and to 65.9% during the follow-up period; 6.6% were prescribed non-ADHD-specific psychotropics concomitantly with atomoxetine. Overall, 40.0% of adults discontinued atomoxetine during the entire follow-up period and 65.9% were persistent with atomoxetine therapy at 3 months post-index date. Mean (SD) atomoxetine medication possession ratio was 0.57 (0.25), and 25.4% switched to an alternative ADHD therapy; methylphenidate (22.4%) and non-ADHD-specific psychotropics (77.6%) were the most common medication alternatives. Nearly 8% augmented atomoxetine with methylphenidates, non-stimulants, or non-ADHD-specific psychotropics. CONCLUSION: In this observational study, a majority of adults with ADHD treated with atomoxetine were still persistent with therapy at 3 months post-index date, with one quarter switching to alternative ADHD therapy. High proportions of mental health comorbidities, along with high use of non-ADHD-specific psychotropic medications in both the baseline and follow-up periods, were observed among patients with ADHD prescribed atomoxetine.