Oncologist Perceptions of Racial Disparity, Racial Anxiety, and Unconscious Bias in Clinical Interactions, Treatment, and Outcomes.

BACKGROUND: Cancer spares no demographic or socioeconomic group; it is indeed the great equalizer. But its distribution is not equal; when structural discrimination concentrates poverty and race, zip code surpasses genetic code in predicting outcomes. Compared with White patients in the United States, Black patients are less likely to receive appropriate treatment and referral to clinical trials, genetic testing, or palliative care/hospice. METHODS: In 2021, we administered a survey to 369 oncologists measuring differences in perceptions surrounding racial disparity, racial anxiety, and unconscious bias and adverse influence on clinical interactions, treatment, and outcomes for non-White patients. We analyzed responses by generational age group, sex/gender, race/ethnicity, US region, and selection of "decline to respond." RESULTS: The most significant differences occurred by age group followed by race/ethnicity. Racial disparity was perceived as moderate to very high by 84% of millennial, 69% of Generation X, and 57% of baby boomer oncologists, who were also 86% more likely than millennials and 63% more likely than Generation Xers to perceive low/nonexistent levels of racial anxiety/unconscious bias. CONCLUSIONS: Most oncologists rarely or never perceived racial anxiety/unconscious bias as adversely influencing clinical treatment or survival outcomes in non-White patients, and White oncologists were 85% more likely than non-White oncologists to perceive rare/nonexistent influence on referral of non-White patients to palliative care/hospice. The discrepancy between 62% of oncologists perceiving moderate to very high levels of racial anxiety/unconscious bias and 37% associating them with adverse influence on non-White patients shows a disconnect, especially among older oncologists (baby boomers), who were also least likely to select the decline option. Together, these factors hinder effective patient-provider communication and result in differential care and outcomes. Oncologists should uncover their own perceptions surrounding racial disparity, racial anxiety, and unconscious bias and modify their behaviors accordingly. It is this simple-and this complicated. Cancer does not discriminate, and neither should cancer care.

Real-world outcomes associated with afatinib use in patients with solid tumors harboring NRG1 gene fusions.

OBJECTIVES: Neuregulin-1 (NRG1) fusions may drive oncogenesis via constitutive activation of ErbB signaling. Hence, NRG1 fusion-driven tumors may be susceptible to ErbB-targeted therapy. Afatinib (irreversible pan-ErbB inhibitor) has demonstrated activity in individual patients with NRG1 fusion-positive solid tumors. This study collected real-world data on demographics, clinical characteristics, and clinical outcomes in this patient population. MATERIALS AND METHODS: In this retrospective, multicenter, non-comparative cohort study, physicians in the US-based Cardinal Health Oncology Provider Extended Network collected data from medical records of patients with NRG1 fusion-positive solid tumors who received afatinib (afatinib cohort) or other systemic therapies (non-afatinib cohort) in any therapy line. Objectives included demographics, clinical characteristics, and outcomes (overall response rate [ORR], progression-free survival [PFS], and overall survival [OS]). RESULTS: Patients (N = 110) with a variety of solid tumor types were included; 72 received afatinib, 38 other therapies. In the afatinib cohort, 70.8 % of patients received afatinib as second-line treatment and Eastern Cooperative Oncology Group performance status (ECOG PS) was 2-4 in 69.4 % at baseline. In the non-afatinib cohort, 94.7 % of patients received systemic therapy as first-line treatment and ECOG PS was 2-4 in 31.6 % at baseline. In the afatinib cohort, ORR was 37.5 % overall (43.8 % when received as first-line therapy); median PFS and OS were 5.5 and 7.2 months, respectively. In the non-afatinib cohort, ORR was 76.3 %; median PFS and OS were 12.9 and 22.6 months, respectively. CONCLUSION: This study provides real-world data on the characteristics of patients with NRG1 fusion-positive solid tumors treated with afatinib or other therapies; durable responses were observed in both groups. However, there were imbalances between the cohorts, and the study was not designed to compare outcomes. Further prospective/retrospective trials are required.

Real-World Effectiveness of Dasatinib Versus Imatinib in Newly Diagnosed Patients With Chronic Myeloid Leukemia.

INTRODUCTION: Limited data exist comparing dasatinib with imatinib in clinical practice. This study assessed real-world outcomes associated with first-line (1L) dasatinib or imatinib treatment of chronic myeloid leukemia (CML). PATIENTS AND METHODS: This retrospective, observational, United States multisite cohort study analyzed electronic medical record data from adults with Philadelphia chromosome-positive (Ph+) CML in the chronic phase (CML-CP) after 1L dasatinib or imatinib between January 2014 and September 2018. Rates of and times to major molecular response (MMR) and deep molecular response (DMR) were assessed overall and in subgroups (low vs. intermediate/high risk, aged <65 vs. ≥65 years, low/normal vs. high body mass index [BMI]). RESULTS: The dasatinib cohort (n = 309) experienced higher rates of MMR (n = 304, 79% vs. 65%, P < .001) and DMR (44% vs. 25%, P < .001) vs. the imatinib cohort with shorter median times to MMR (11.9 vs. 14.7 months, P < .001) and DMR (30.3 vs. 66.1 months, P < .001). Patients with intermediate-/high-risk disease and those aged <65 years had higher MMR and DMR rates and achieved response earlier with dasatinib (P < .01). Patients with low-risk disease treated with dasatinib had higher rates of DMR (60% vs. 32%, P = .01). Across BMI strata, rates of MMR and DMR were higher with dasatinib (P < .05). CONCLUSIONS: Patients with CML-CP treated with 1L dasatinib achieved higher rates of, with shorter times to, MMR and DMR versus 1L imatinib. These clinically meaningful improvements were observed across subgroups.

Real-world clinical outcomes with enasidenib in relapsed or refractory acute myeloid leukemia.

Enasidenib was approved by the Food and Drug Administration in 2017 for the treatment of patients with relapsed or refractory (RR) acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation. Given limited data in clinical practice, this study assessed real-world clinical outcomes and healthcare resource use in patients with RR AML. Physicians performed chart abstraction of patients with RR IDH2-mutated AML treated with enasidenib (between 1/2018 and 6/2019) or other first-line (1 L) RR therapy (between 1/2016 and 7/2017). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and adjusted risk of progression and death were estimated by multivariable Cox proportional hazard models. Among 124 patients treated with enasidenib and 76 patients treated with other 1 L RR therapy, overall response rate was higher among patients treated with enasidenib vs. other 1 L RR therapies (77% vs. 52%, p < 0.01). After a median follow-up of 9 and 6 months, median PFS was 8 months in enasidenib-treated patients and 5 months in patients receiving other 1 L RR therapy, respectively (adjusted HR=0.36, 95% CI: 0.23-0.57, p < 0.01). Median OS was 11 and 6 months in enasidenib-treated patients and patients receiving other 1 L RR therapy, respectively (adjusted HR=0.37, 95% CI: 0.22-0.60, p < 0.01). Fewer enasidenib-treated patients were hospitalized during 1 L RR therapy vs. those receiving other therapies (14% vs. 46%, p < 0.01). Results from this real-world study confirm the effectiveness of enasidenib among patients with IDH2-mutated RR AML and demonstrate that hospitalizations were significantly lower vs. other 1 L RR treatment in clinical practice.

Treatment Patterns of Real-World Patients with TRK Fusion Cancer Treated by US Community Oncologists.

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are present across various tumor types with an estimated overall prevalence of less than 1%. Tropomyosin receptor kinase inhibitors (TRKis) block the constitutively activated tyrosine receptor kinase (TRK) fusion protein produced in cancers with NTRK gene fusions (NTRK+) from downstream signaling. Many treatment guidelines now include TRKis as first-line (1L) or subsequent treatment options for TRK fusion cancer. OBJECTIVE: This study aimed to assess treatment patterns subsequent to a finding of NTRK+ status among patients with TRK fusion cancer. PATIENTS AND METHODS: This was a one-time, retrospective, multi-site patient chart abstraction by oncology practices in the USA from June to September 2020. US medical oncologists from the Oncology Provider Extended Network (OPEN) who had treated patients with NTRK+ advanced/metastatic solid tumors abstracted information into electronic case report forms (eCRFs) for adult patients with advanced/metastatic solid tumors and a NTRK+ tumor test result with a known fusion partner. Data abstracted into eCRFs by oncologists included demographic, clinical, and treatment characteristics of patients with advanced/metastatic TRK fusion solid tumors. Responses were summarized using descriptive statistics. Median treatment durations across the lines of therapy were estimated by Kaplan-Meier time to discontinuation. RESULTS: A total of 19 medical oncologists abstracted data from 110 patient charts. Median patient age at advanced/metastatic diagnosis was 62 years. The majority of patients were male (58.2%) and White (79.1%). Solid tumor types reported in at least 10% of the study cohort were lung (24.5%), cholangiocarcinoma (13.6%), pancreatic (10.9%), and colorectal (10.0%). Results for patients with hepatobiliary cancers (i.e., cholangiocarcinoma, pancreatic cancer, hepatocellular carcinoma) and colorectal cancer, and appendiceal cancer are also included. Median duration of 1L TRKi therapy was 16.8 months across all solid tumor types, whereas median duration of 1L was 5.6 months among patients receiving non-TRKi therapies (p = 0.017). Among the solid tumor types represented by at least 10% of the study population, median duration of 1L TRKi therapy was only reached in patients with pancreatic cancer (3.3 months). Median duration of TRKi in the second-line (2L) setting was 7.9 months overall, relative to 5.3 months among patients receiving non-TRKi therapies (p = 0.003). Across lung, cholangiocarcinoma, pancreatic, and colorectal cancers, the median durations of 2L TRKi therapy were 14.1, 6.0, 6.1, and 4.1 months, respectively. CONCLUSION AND RELEVANCE: Among patients with advanced/metastatic TRK fusion solid tumors, medical oncologists reported that approximately two-thirds initiated a TRKi during the study period. Treatment with a TRKi was longer in duration compared to non-TRKi treatment in 1L and 2L therapy. Additional research is needed to gain insight into the association between early TRKi therapy initiation and clinical outcomes in the real-world setting.

Timing of NTRK Gene Fusion Testing and Treatment Modifications Following TRK Fusion Status Among US Oncologists Treating TRK Fusion Cancer.

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers with an estimated prevalence of less than 1% across all solid tumors. Tropomyosin receptor kinase inhibitors (TRKis) block the constitutively activated tyrosine receptor kinase (TRK) fusion protein produced in NTRK gene fusion positive (NTRK+) tumors from downstream signaling. Tropomyosin receptor kinase inhibitors are now first-line (1L) or subsequent treatment options for TRK fusion cancers. OBJECTIVE: This study assessed timing of NTRK gene fusion testing and treatment modifications among patients with TRK fusion cancers. PATIENTS AND METHODS: This was a one-time physician questionnaire with a retrospective, multisite patient chart abstraction of oncology practices in the USA. From June to September 2020, medical oncologists from the Oncology Provider Extended Network (OPEN) who treated patients with NTRK+ advanced/metastatic solid tumors abstracted information into electronic case report forms (eCRFs) for adult patients with advanced/metastatic solid tumors and a NTRK+ tumor test result with a known fusion partner. Use of NTRK testing in routine clinical practice among patients with advanced/metastatic solid tumors was assessed. Data included demographic, clinical, and NTRK gene fusion testing characteristics. Responses were summarized using descriptive statistics. RESULTS: Twenty-eight community-based medical oncologists who had managed or treated 148 patients with advanced/metastatic TRK fusion cancer between 01/01/2016 and 12/31/2019 completed the survey. Lung (27%), thyroid (18%), salivary gland (14%), and colorectal (12%) were the most commonly reported tumor types. A majority (68%) tested NTRK status prior to 1L initiation; testing after disease progression on 1L (36%), 2L (25%), and 3L (21%) was also noted. Most oncologists (96%) reported no difficulty interpreting NTRK reports. Nearly all (96%) indicated using next-generation sequencing (NGS) for determining NTRK status. The majority (57%) indicated that age, tumor type, and performance status did not impact NTRK testing decisions. Less than half (46%) include TRKi therapy following NTRK+ determination. NTRK testing guidelines were commonly reviewed by physicians (89%). CONCLUSION AND RELEVANCE: Among patients with advanced/metastatic TRK fusion cancer, medical oncologists reported testing for NTRK fusions at diagnosis or prior to 1L. Future research should elucidate why fewer than half of oncologists surveyed (46%) would not use TRKis after NTRK+ status confirmation, assess clinical practices among NTRK+ patients, and characterize treatment patterns and clinical outcomes in real-world settings.

Real-world Treatment Patterns and Reasons for Therapy Selection in Patients with Advanced Hepatocellular Carcinoma in US Oncology Practices.

BACKGROUND: The treatment landscape for advanced hepatocellular carcinoma (aHCC) is rapidly expanding beyond tyrosine kinase inhibitors (TKIs) in the first-line (1L) setting, with multiple TKIs and immune-checkpoint inhibitors (ICIs) now being evaluated in combination. Real-world evidence describing current treatment patterns and reasons for 1L and 2L treatment selection in aHCC is sparse. PATIENTS AND METHODS: A retrospective cohort study with a cross-sectional survey element was conducted using Cardinal Health's Oncology Provider Extended Network. U.S. medical oncologists identified adult aHCC patients initiating 1L systemic therapy between January 1, 2017 and July 31, 2019 and abstracted data from patient medical records. Data included provider characteristics, patient demographics and clinical characteristics, treatment regimens, and physician rationale for treatment regimen choice. RESULTS: A total of 44 medical oncologists provided data on 284 aHCC patients. The median age at 1L initiation was 61.5 years, and the majority were male (78%) and white (66%). Nearly half (47%) initiated 1L treatment in 2019, 34% were ECOG performance status 2+, and 63% were Child-Pugh Class B/C. Among the 284 aHCC patients, TKIs were used by 94% of patients in the 1L setting, comprised predominantly of sorafenib (54%) and lenvatinib (38%). ICIs were most common among the 90 patients (66%) who received 2L treatment. CONCLUSION: In the community-oncology practice setting, nearly all aHCC patients received sorafenib or lenvatinib in the 1L setting, while the majority of patients received an ICI in the 2L setting. With recent ICI approvals in aHCC, this marks the beginning of an increased use of ICIs in the 1L setting.

Comparison of Solid Tumor Treatment Response Observed in Clinical Practice With Response Reported in Clinical Trials.

Importance: In clinical trials supporting the regulatory approval of oncology drugs, solid tumor response is assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Calculation of RECIST-based responses requires sequential, timed imaging data, which presents challenges to the method's application in real-world evidence research. Objective: To evaluate the feasibility and validity of a novel real-world RECIST method in assessing tumor burden associated with therapy for a large heterogeneous patient population undergoing treatment in routine clinical practice. Design, Setting, and Participants: This cohort study used physician-abstracted data pooled from retrospective, multisite electronic health record (EHR) review studies of patients treated with anticancer drugs at US oncology practices from 2014 through 2017. Included patients were receiving first-line treatment for thyroid cancer, breast cancer, or metastatic melanoma. Data were analyzed from March through August 2020. Exposures: Undergoing treatment with immunotherapy or targeted therapy. Main Outcomes and Measures: Tumor response was classified according to RECIST guidelines (ie, change in sum diameter of target lesions) post hoc with measurements derived from imaging scans and reports. Results: Among 1308 completed electronic case report forms, 956 forms (73.1%) had adequate data to classify real-world RECIST response. The greatest difference between physician-recorded responses and real-world RECIST-based responses was found in the proportion of complete responses: 118 responses (12.3%) vs 46 responses (4.8%) (P < .001). Among 609 patients in the metastatic melanoma population, complete responses were reported in 112 physician-recorded responses (18.4%) vs 44 real-world RECIST-based responses (7.2%) (P < .001), compared with 11 of 247 responses (4.5%) to 31 of 192 responses (16.1%) across pivotal trials of the same melanoma therapies. Conclusions and Relevance: These findings suggest that comparing tumor lesion sizes and categorizing treatment response according to RECIST guidelines may be feasible using real-world data. This study found that physician-recorded assessments were associated with overestimation of treatment response, with the largest overestimation among complete responses. Real-world RECIST-based assessments were associated with better approximations of tumor response reported in clinical trials compared with those reported in EHRs.

Real-world adverse events associated with CAR T-cell therapy among adults age ≥ 65 years.

INTRODUCTION: Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for relapsed or refractory large B-cell lymphoma (LBCL) with the Food and Drug Administration (FDA) approvals of axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel). Although the incidence of LBCL is highest among patients age ≥ 65, clinical trials supporting approval of these 2 products primarily enrolled younger patients. Safety data for axi-cel and tis-cel in older patients is limited. METHODS: In this analysis, we queried the FDA Adverse Events Reporting System (FAERS) database for cases associated with axi-cel or tis-cel from the FDA approval dates for the LBCL indication for each product through December 31, 2019, and compared adverse events (AEs) reported for cases involving patients aged <65 and ≥ 65. RESULTS: A total of 804 cases were retrieved, with 333 (41%) involving patients age ≥ 65. Cytokine release syndrome (CRS) was the most common AE reported in both age groups. Cases involving older patients had a significantly higher proportion of neurological AEs, including CAR T-cell-related encephalopathy syndrome (8% vs. 4%, p = 0.03). Some individual clinical features of CRS were significantly more common among younger age group cases, including pyrexia (33% vs. 23%, p < 0.01), tachycardia (10% vs. 5%, p < 0.01), and thrombocytopenia (4% vs. 2%, p = 0.03). DISCUSSION: In this age-based analysis of FAERS reports for patients treated with axi-cel or tis-cel, we identified differences in patterns of AEs experienced. This large-scale post-marketing study complements clinical trial safety data and may help inform clinicians' decision making when treating adult patients with CAR-T cell therapy.

Neurological adverse events following CAR T-cell therapy: a real-world analysis.

Aim: To characterize real-world neurological adverse events (AEs) associated with chimeric antigen receptor T-cell therapies in patients with refractory/relapsed large B-cell lymphomas. Materials & methods: Postmarketing case reports from the US FDA AEs reporting system involving axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) for large B-cell lymphomas were analyzed. Results: Of 804 AE cases identified (637 axi-cel, 167 tisa-cel), 428 (67%) of axi-cel cases and 43 (26%) of tisa-cel cases reported neurological AEs. Compared with cases without neurological AEs, significant associations were observed between neurological AEs and use of axi-cel, age ≥65 years, and the outcome of hospitalization. Conclusion: Neurological AEs were common with chimeric antigen receptor T-cell therapy in the real world and largely reflected those reported in clinical trials.

Frequency and Causes of Burnout in US Community Oncologists in the Era of Electronic Health Records.

BACKGROUND: Physician burnout, characterized by exhaustion of physical or emotional strength, cynicism, and lack of achievement, has become a worsening phenomenon in medicine, contributing to higher health care costs and patient/physician dissatisfaction. How burnout has affected hematologists and oncologists is not well studied. METHODS: US community oncologists/hematologists were queried via a Web-based survey from September-November 2018. Physicians were asked about frequency of burnout symptoms, drivers of work-related stress, and their perceptions on management of workload. RESULTS: Among the 163 physicians surveyed, 46% felt a substantial amount of stress at work. Most physicians felt emotionally (85%) and physically (87%) exhausted. A majority of physicians felt lethargic (67%), ineffective (64%), and/or detached (63%). In a typical workweek, 93% needed time beyond time allocated to clinical care to complete work responsibilities. Electronic health record (EHR) responsibilities caused moderate to excessive stress at work for 67% of physicians; 79% of physicians worked on EHRs outside of clinic hours. Other sources of excessive stress were changing reimbursement models (33%), interactions with payers (31%), and increasing patient and caregiver demands (31%). A third of physicians have considered retiring early or changing their career path to cope. To combat burnout, physicians' practices have used advanced practice providers, invested in information technology, and/or hired additional administrative staff. However, the majority of physicians stated they had optimal or good control over their workload. CONCLUSION: Most oncologists experience burnout symptoms and require additional time beyond that allocated to clinical care to complete their workload. The discordance between oncologists' admission of stress and exhaustion while claiming good control over those same burdens warrants exploration in future research.

Real-world outcomes among patients with early rapidly progressive rheumatoid arthritis.

OBJECTIVES: To characterize treatment patterns, healthcare resource utilization (HRU), and disease activity among patients with early rapidly progressive rheumatoid arthritis (eRPRA) in the United States when treated with a first-line biologic disease-modifying antirheumatic drug (bDMARD) tumor necrosis factor-α (TNF) inhibitor or first-line abatacept. STUDY DESIGN: Observational, multicenter, retrospective, longitudinal, medical records-based, cohort study. METHODS: Patients with eRPRA were identified by anti-citrullinated protein antibody positivity, 28-joint Disease Activity Score-C-reactive protein of 3.2 or greater, symptomatic synovitis in 2 or more joints for at least 8 weeks prior to the index date, and onset of symptoms within 2 years or less of the index date. Patients received abatacept or a TNF inhibitor as first-line treatment. Patient characteristics, treatment patterns, HRU, and disease activity following bDMARD initiation were compared across the 2 groups. Odds ratios (ORs) of HRU in the first 6 months of bDMARD treatment were estimated using multivariable logistic regression to adjust for patient mix. RESULTS: There were 60 patients treated with abatacept and 192 treated with a TNF inhibitor in the first line. Those treated with first-line abatacept had lower adjusted odds of hospitalization (OR, 0.42; 95% CI, 0.18-0.95), emergency department (ED) visits (OR, 0.39; 95% CI, 0.16-0.93), and magnetic resonance imaging (MRI) (OR, 0.45; 95% CI, 0.21-0.97) than those treated with a first-line TNF inhibitor (all P <.05). Adjusted odds of achieving low disease activity as measured by clinical disease activity index within 100 days of bDMARD initiation favored first-line abatacept versus a first-line TNF inhibitor (OR, 4.37; 95% CI, 1.34-13.94; P = .01). CONCLUSIONS: Adjusting for disease severity, patients with eRPRA who were treated with first-line abatacept were less likely to have hospitalizations, ED visits, and MRI use during the first 6 months of bDMARD treatment and more likely to achieve low disease activity within 100 days of bDMARD start compared with those who received a first-line TNF inhibitor.

Patterns of Care Among Real-World Patients with Metastatic Neuroendocrine Tumors.

BACKGROUND: Although recent pivotal trials (PROMID, CLARINET) have established somatostatin analogs (SSAs) as first-line agents for neuroendocrine tumors (NETs), their use in clinical practice is largely unknown. We aimed to understand real-world management and treatment of gastroenteropancreatic (GEP) NETs. MATERIALS AND METHODS: Patients with metastatic GEP-NETs treated with SSAs, lanreotide depot or octreotide long-acting release (LAR), between January 1, 2015, and December 31, 2015, were identified from a U.S. claims database supplemented with chart review for a subset of patients. Descriptive statistics summarized patients' demographics, clinical characteristics, treatment patterns, and healthcare resource use. Univariate and multivariate comparisons were made across SSA groups. RESULTS: Among 548 patients treated with an SSA for metastatic GEP-NET (lanreotide = 108; octreotide = 440), demographic and clinical characteristics were similar across groups, except more patients with pancreatic NETs were treated with lanreotide (38.7% vs. 6.3%, p < .01). More octreotide patients had a diagnosis of carcinoid syndrome compared with lanreotide patients (19.8% vs. 11.1%, p = .02). Approximately 1.1% of patients received lanreotide (>120 mg every 4 weeks [Q4W]) at a dose above label compared with 12.7% of octreotide patients (>30 mg Q4W; p < .01). At 1.5 years after SSA initiation, 85.7% (95% confidence interval, 74.3%-92.3%) were still on index SSA as reported by the physician. Variances between chart review and claims data were significant. CONCLUSION: SSAs were common in first-line systemic intervention, but dose escalations and dosing deviations outside of label were noted. Variances between claims and chart review warrant additional research to compare methodologies. With an increasing focus on value-based care in oncology, it is critical to understand the use of, and outcomes with, these agents in community practices. IMPLICATIONS FOR PRACTICE: The aim of this study was to enhance understanding of real-world management and treatment of metastatic neuroendocrine tumors (NETs), with particular focus on systemic therapy with a somatostatin analog (SSA). As per published guidelines, SSAs are common in first-line systemic intervention, but dose escalations and dosing deviations outside of the label are noted for symptom control. Nevertheless, oncologists must weigh the implications of the use of above-label dosing of SSAs to manage and treat patients with metastatic NET within a value-based care framework.

Health Care Resource Utilization and Costs in First-Line Treatments for Patients with Metastatic Melanoma in the United States.

BACKGROUND: The treatment landscape for patients with metastatic melanoma has changed dramatically with the introduction of novel therapies, such as targeted therapies and immunotherapies, in recent years. Health care resource utilization (HCRU) and cost data are needed to further evaluate these treatments in a value-based health care system. OBJECTIVE: To examine HCRU and total cost of care among U.S. metastatic melanoma patients treated with first-line systemic therapies, including immunotherapies, targeted therapies, and chemotherapy. METHODS: A retrospective observational study was conducted using a U.S. claims database. Adults with ≥ 2 claims for melanoma and ≥ 1 claim for metastasis between January 1, 2012, and June 30, 2017, were identified. Patients had pharmacy and medical enrollment ≥ 6 months before and ≥ 3 months following first-line treatment start. Per patient per month (PPPM) HCRU and costs were calculated by first-line treatment drug class: PD-1 inhibitors, CTLA-4 inhibitors, CTLA-4 + PD-1 combination, BRAF monotherapy, BRAF + MEK combination, and chemotherapy. Adjusted odds ratios (ORs) for HCRU were estimated by logistic regressions and adjusted costs were estimated by generalized linear models using log-link with gamma distribution to control for differences in patient characteristics across groups. RESULTS: Among 1,599 metastatic melanoma patients (PD-1, n = 255; CTLA-4, n = 555; CTLA-4 + PD-1, n = 88; BRAF, n = 210; BRAF + MEK, n=102; chemotherapy=389), mean age ranged from 59-68 years, and the majority were male (62%). Any hospitalization during first-line treatment was less frequent among PD-1-treated patients (25.9%) compared with 34.7%-45.5% of all other groups (all P < 0.05). PPPM hospitalizations were lowest in PD-1 (0.06) compared with 0.09-0.16 across all other groups (all P < 0.05), and PPPM emergency department (ED) visits were lowest in PD-1 (0.09) compared with 0.13-0.18 across all other groups (all P < 0.05), except for BRAF + MEK (0.14, P = 0.08). CTLA-4, CTLA-4 + PD-1, and BRAF + MEK had increased odds of hospitalization compared to PD-1 (adjusted ORs = 2.10, 2.35, 2.15, respectively; all P < 0.05). Total adjusted PPPM costs were significantly lower for PD-1 ($13,059) compared with CTLA-4 ($25,583), CTLA-4 + PD-1 ($31,310), and BRAF + MEK ($21,517) and higher compared to BRAF ($8,158) and chemotherapy ($6,361). CONCLUSIONS: Hospitalizations and ED visits represent important HCRU for metastatic melanoma patients and were lowest among PD-1-treated patients compared with any other systemic therapies (except for ED visits when compared with BRAF + MEK). Total monthly costs varied substantially across first-line regimens and were significantly lower in PD-1-treated patients compared with patients treated with CTLA-4, CTLA-4 + PD-1, and BRAF + MEK. DISCLOSURES: This study was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. Klink, Feinberg, and Nero are employees of Cardinal Health Specialty Solutions, which received funding from Merck to conduct this study. Chmielsowki is a consultant to Merck but received no funding for the development of this manuscript. Ahsan and Liu are employees of Merck. Chmielowski reports advisory board/speaker fees from Bristol-Myers Squibb, Merck, Genentech/Roche, Iovance Biotherapeutics, HUYA Bioscience International, Compugen, Array BioPharma, Regeneron, Biothera, Janssen, and Novartis. Ahsan has a patent (US20160008380A1) pending.

Treatment sequence of lenalidomide and hypomethylating agents and the impact on clinical outcomes for patients with myelodysplastic syndromes.

Lenalidomide and hypomethylating agents (HMAs) azacitidine and decitabine are approved for treating myelodysplastic syndromes (MDS), but optimal sequencing is unclear. Adults with MDS were identified from a US payer claims database (Inovalon MORE2 Registry) to compare outcomes with lenalidomide followed by HMA (LEN-HMA) or HMA followed by lenalidomide (HMA-LEN). There were 96 patients who received LEN-HMA and 89 who received HMA-LEN. LEN-HMA-treated patients had a longer time to second treatment discontinuation (29.0 vs. 19.0 months, p=.009; adjusted hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.29-0.91, p=.023). LEN-HMA-treated patients had a longer median time to insurance disenrollment (22.4 vs. 16.1 months, p<.001; adjusted HR 0.64, 95% CI: 0.44-0.92, p=.017), used as a proxy for survival. Longer treatment duration and survival with LEN-HMA support first-line use of lenalidomide in MDS in sequence with HMAs.

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

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

Histological features of ileitis differentiating pediatric Crohn disease from ulcerative colitis with backwash ileitis.

BACKGROUND/AIM: Pediatric ileocolonic Crohn disease (CD) may be difficult to distinguish from ulcerative colitis (UC) with backwash ileitis (BWI). The primary aim of the study was to determine the probability of CD in children with a confluent colitis and ileitis when newly diagnosed with inflammatory bowel disease (IBD). METHODS: A retrospective observational study of 100 newly diagnosed patients with IBD was performed. Two pathologists reviewed ileal biopsy specimens for 8 histological features. Biopsy and clinical features were evaluated for predictive ability of a final diagnosis of CD. RESULTS: The presence of crypt distortion, lamina propria (LP) expansion, and acute LP inflammation combined with 4 clinical variables in multivariate regression analysis had adequate discriminative validity when comparing the mean probability of a final CD diagnosis between CD and not-CD groups (0.90 vs. 0.59, p value <0.001). When crypt distortion, LP expansion, and acute LP inflammation are present in any combination, the sensitivity and specificity for presence of CD ranges 38.4-57% and 92.9-100%, respectively. CONCLUSIONS: Combining histological features of ileitis and clinical variables can adequately discriminate between the presence and absence of Crohn disease in children who present with confluent colitis and ileitis. Combined presence of certain histological features has high specificity for CD.

Economic burden of hepatitis B infection among patients with diabetes.

Despite ACIP recommendation and cost-effectiveness established in those 19-59 y old diabetes patients the uptake of Hepatitis B vaccine in diabetes patients is low. There is need to highlight the impact of Hepatitis B virus (HBV) infection in diabetes patients in terms of healthcare utilization and costs to recognize the burden of HBV in this population. This retrospective claims analysis included patients with diabetes and HBV (cases; n=1,236) and those with diabetes without HBV (controls; n=4,944), identified by ICD-9-CM diagnosis codes. Cases were matched with 4 controls using propensity score matching. Healthcare utilization and cost were compared; incremental effect of HBV infection was assessed using multivariate analysis. In the adjusted analyses, the mean number of hospitalizations (0.6 vs 0.4), outpatient service visits (34.2 vs. 20.4), and office visits (10.9 vs. 9.8) were 41%, 68%, and 11% higher, respectively, in cases vs. controls (all p<0.05). Gastroenterologist visits (0.8 vs. 0.2) and infectious disease visits (0.1 vs. 0.0) were 80% and 18% higher in subset of case and controls with these events. Cases ($39,435) incurred $16,397 incremental total costs compared with controls ($23,038). Medical ($30,968 vs. $17,765) and pharmacy costs ($8,029 vs. $5,114) were both significantly higher for cases (p < 0.0001). Healthcare utilization and costs were higher among patients with diabetes and HBV than in those with diabetes alone. These results provide evidence supporting the need for HBV vaccination among unvaccinated diabetes patients.

Detection of enthesitis in children with enthesitis-related arthritis: dolorimetry compared to ultrasonography.

OBJECTIVE: To evaluate the distribution of enthesitis and the accuracy of physical examination with a dolorimeter for the detection of enthesitis in children, using ultrasound (US) assessment as the reference standard. METHODS: We performed a prospective cross-sectional study of 30 patients with enthesitis-related arthritis (ERA) and 30 control subjects. The following tendon insertion sites were assessed by standardized physical examination with a dolorimeter and US: common extensor on the lateral humeral epicondyle, common flexor on the medial humeral epicondyle, quadriceps at the superior patella, patellar ligament at the inferior patella, Achilles, and plantar fascia at the calcaneus. RESULTS: Abnormal findings on US were detected most commonly at the insertion of the quadriceps (30% [18 of 60 sites]), common extensor (12% [7 of 60]), and Achilles (10% [6 of 60]) tendons. The intrarater reliability of US (kappa statistic) was 0.78 (95% confidence interval [95% CI] 0.63-0.93), and the interrater reliability was 0.81 (95% CI 0.67-0.95). Tenderness as detected by standardized dolorimeter examination had poor positive predictive value for US-confirmed enthesitis. In comparison to controls, patients with ERA reported more pain and had lower pain thresholds at every site, including control sites (P < 0.001 for all comparisons). The interrater reliability of dolorimeter examination for detection of enthesitis was low (κ = 0.49 [95% CI 0.33-0.65]). CONCLUSION: Compared to US, standardized dolorimeter examination for the detection of enthesitis in children has poor accuracy and reliability. The decreased pain threshold of ERA patients likely contributed to the limited accuracy of the physical examination findings. Further research regarding the utility of US for identifying enthesitis at diagnosis of juvenile idiopathic arthritis, accurately predicting disease progression, and guiding therapeutic decisions is warranted.