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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.
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Neoplasias , Oncólogos , Humanos , Ansiedad/etiología , Ansiedad/terapia , Sesgo Implícito , Negro o Afroamericano , Neoplasias/terapia , Estados Unidos , Blanco , Adulto , Persona de Mediana Edad , Anciano , Grupos RacialesRESUMEN
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.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Carcinoma Hepatocelular/tratamiento farmacológico , Estudios Transversales , Femenino , Humanos , Lactante , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Sorafenib/uso terapéuticoRESUMEN
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.
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Tumores Neuroendocrinos/terapia , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Tumores Neuroendocrinos/secundario , Estudios RetrospectivosRESUMEN
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.
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Antineoplásicos/uso terapéutico , Carcinoma de Células de Merkel/tratamiento farmacológico , Registros Electrónicos de Salud/estadística & datos numéricos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células de Merkel/diagnóstico por imagen , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Oncólogos/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Cutáneas/diagnóstico por imagen , Encuestas y Cuestionarios/estadística & datos numéricos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
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.
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Antineoplásicos , Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia Mieloide de Fase Crónica , Adulto , Humanos , Dasatinib/uso terapéutico , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Estudios Retrospectivos , Estudios de Cohortes , Pirimidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Resultado del Tratamiento , Antineoplásicos/uso terapéuticoRESUMEN
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.
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Neoplasias Pulmonares , Humanos , Afatinib/uso terapéutico , Afatinib/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Retrospectivos , Estudios de Cohortes , Fusión Génica , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Neurregulina-1/genéticaRESUMEN
BACKGROUND/OBJECTIVES: The phase 3 REGAIN study and its open-label extension demonstrated the efficacy of the complement C5 inhibitor eculizumab in patients with treatment-refractory, acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG). The aim of the ELEVATE study was to assess the effectiveness of eculizumab in clinical practice in adults with MG in the United States. METHODS: A retrospective chart review was conducted in adults with MG who initiated eculizumab treatment between October 23, 2017 and December 31, 2019. Outcomes assessed before and during eculizumab treatment using a pre- versus post-treatment study design included Myasthenia Gravis-Activities of Daily Living (MG-ADL) total scores; minimal symptom expression (MSE); physician impression of clinical change; minimal manifestation status (MMS); and concomitant medication use. RESULTS: In total, 119 patients were included in the study. A significant reduction was observed in mean MG-ADL total score, from 8.0 before eculizumab initiation to 5.4 at 3 months and to 4.7 at 24 months after eculizumab initiation (both p < 0.001). At 24 months after eculizumab initiation, MSE was achieved by 19% of patients. MMS or better was achieved by 30% of patients at 24 months. Additionally, 64% of patients receiving prednisone at eculizumab initiation had their prednisone dosage reduced during eculizumab treatment and 13% discontinued prednisone; 32% were able to discontinue nonsteroidal immunosuppressant therapy. DISCUSSION: Eculizumab treatment was associated with sustained improvements in MG-ADL total scores through 24 months in adults with MG. Prednisone dosage was reduced in approximately two-thirds of patients, suggesting a steroid-sparing effect for eculizumab.
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PURPOSE: Therapeutic plasma exchange (TPE) has been increasingly used over the past decade as a first-line and lifesaving treatment for various conditions classified by the American society for apheresis (ASFA). To date, the degree to which utilization of TPE in pediatrics mirrors recommendations is unknown. METHODS: Using inpatient administrative data from 42 children's hospitals we conducted an 8-year retrospective cohort study of children (≤18 years) with an international classification of diseases-9-clinical modification (ICD-9-CM) discharge diagnosis indicating an ASFA Category I or II condition, or a procedure code indicating receipt of TPE during hospitalization. RESULTS: TPE was performed during 4,190 hospitalizations of 3,449 patients, of whom 310 (9.0%) and 77 (2.2%) had a primary discharge diagnosis of an ASFA Category I or II condition, respectively. Rates of TPE use for Category I conditions were highest for children with thrombotic thrombocytopenic purpura (TTP), Goodpasture's syndrome, and myasthenia gravis. TPE use in children's hospitals significantly increased from 2003 to 2010, but TPE was performed during only 13.4 and 9.3% of hospitalizations for ASFA Category I and II conditions, respectively. There was significant between-hospital variation in the use of TPE for Category I conditions as a group and individual Category I conditions including TTP. CONCLUSION: We found low levels of TPE use across hospitals for key indications, including TTP, a condition for which TPE is considered a first-line and life-saving procedure. The variation identified may contribute to varying clinical outcomes between hospitals, warrants further investigation, and represents an important opportunity to improve quality of care.
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Enfermedades Autoinmunes/terapia , Hospitales Pediátricos/estadística & datos numéricos , Intercambio Plasmático/estadística & datos numéricos , Lesión Renal Aguda/terapia , Adolescente , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Niño , Preescolar , Grupos Diagnósticos Relacionados , Encefalitis/terapia , Femenino , Humanos , Lactante , Clasificación Internacional de Enfermedades , Masculino , Miastenia Gravis/terapia , Intercambio Plasmático/tendencias , Púrpura Trombocitopénica Trombótica/terapia , Grupos Raciales , Insuficiencia Respiratoria/terapia , Estudios Retrospectivos , Resultado del Tratamiento , Estados UnidosRESUMEN
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.
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Colangiocarcinoma , Neoplasias , Oncólogos , Neoplasias Pancreáticas , Adulto , Colangiocarcinoma/tratamiento farmacológico , Femenino , Fusión Génica , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología , Proteínas de Fusión Oncogénica/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptor trkA/genética , Receptor trkA/metabolismo , Estudios Retrospectivos , Tropomiosina/genética , Tropomiosina/uso terapéutico , Neoplasias PancreáticasRESUMEN
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.
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Isocitrato Deshidrogenasa , Leucemia Mieloide Aguda , Humanos , Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/inducido químicamente , Aminopiridinas/uso terapéutico , Aminopiridinas/efectos adversos , Triazinas/uso terapéutico , Triazinas/efectos adversos , MutaciónRESUMEN
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.
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Neoplasias , Oncólogos , Proteínas Tirosina Quinasas Receptoras/metabolismo , Adulto , Fusión Génica , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología , Proteínas de Fusión Oncogénica/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptor trkA/genética , Receptor trkA/metabolismo , Estudios Retrospectivos , Tropomiosina/genética , Tropomiosina/uso terapéuticoRESUMEN
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.
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Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Melanoma/tratamiento farmacológico , Criterios de Evaluación de Respuesta en Tumores Sólidos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias de la Tiroides/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/patología , Carcinoma/diagnóstico por imagen , Carcinoma/secundario , Ensayos Clínicos como Asunto , Estudios de Factibilidad , Femenino , Humanos , Masculino , Melanoma/diagnóstico por imagen , Melanoma/secundario , Terapia Molecular Dirigida , Nivolumab/uso terapéutico , Variaciones Dependientes del Observador , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Neoplasias de la Tiroides/patología , Resultado del Tratamiento , Carga TumoralRESUMEN
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 ageâ¯≥â¯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 andâ¯≥â¯65. RESULTS: A total of 804 cases were retrieved, with 333 (41%) involving patients ageâ¯≥â¯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%, pâ¯=â¯0.03). Some individual clinical features of CRS were significantly more common among younger age group cases, including pyrexia (33% vs. 23%, pâ¯<â¯0.01), tachycardia (10% vs. 5%, pâ¯<â¯0.01), and thrombocytopenia (4% vs. 2%, pâ¯=â¯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.
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Linfoma de Células B Grandes Difuso , Trombocitopenia , Anciano , Humanos , Inmunoterapia AdoptivaRESUMEN
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.
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Agotamiento Profesional , Oncólogos , Agotamiento Profesional/epidemiología , Registros Electrónicos de Salud , Humanos , Encuestas y Cuestionarios , Carga de TrabajoRESUMEN
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.
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Antineoplásicos Inmunológicos/efectos adversos , Productos Biológicos/efectos adversos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/inducido químicamente , Receptores de Antígenos de Linfocitos T/uso terapéutico , Receptores Quiméricos de Antígenos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/uso terapéutico , Productos Biológicos/uso terapéutico , Femenino , Humanos , Linfoma de Células B Grandes Difuso/inmunología , Masculino , Persona de Mediana Edad , Linfocitos T/efectos de los fármacos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To describe variation regarding inpatient therapy and evaluation of children with Henoch Schönlein purpura (HSP) admitted to children's hospitals across the United States. STUDY DESIGN: We conducted a retrospective cohort study of children discharged with a diagnosis of HSP between 2000 and 2007 by use of inpatient administrative data from 36 children's hospitals. We examined variation among hospitals in the use of medications, diagnostic tests, and intensive care services with multivariate mixed effects logistic regression models. RESULTS: During the initial HSP hospitalization (n = 1988), corticosteroids were the most common medication (56% of cases), followed by opioids (36%), nonsteroidal antiinflammatory drugs (35%), and antihypertensive drugs (11%). After adjustment for patient characteristics, hospitals varied significantly in their use of corticosteroids, opioids, and nonsteroidal antiinflammatory drugs; the use of diagnostic abdominal imaging, endoscopy, laboratory testing, and renal biopsy; and the use of intensive care services. By contrast, hospitals did not differ significantly regarding administration of antihypertensive drugs or performance of skin biopsy. CONCLUSIONS: The significant variation identified may contribute to varying HSP clinical outcomes between hospitals, warrants further investigation, and represents a potentially important opportunity to improve quality of care.
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Hospitalización , Hospitales Pediátricos , Vasculitis por IgA/diagnóstico , Vasculitis por IgA/terapia , Pautas de la Práctica en Medicina , Adolescente , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Vasculitis por IgA/complicaciones , Lactante , Modelos Logísticos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Estados UnidosRESUMEN
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.
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Antimetabolitos Antineoplásicos/uso terapéutico , Lenalidomida/uso terapéutico , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/mortalidad , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Toma de Decisiones Clínicas , Manejo de la Enfermedad , Femenino , Humanos , Lenalidomida/administración & dosificación , Masculino , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/etiología , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
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.
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Atención a la Salud/economía , Melanoma/economía , Anciano , Antígeno CTLA-4/metabolismo , Femenino , Costos de la Atención en Salud , Recursos en Salud , Hospitalización/economía , Humanos , Inmunoterapia/economía , Masculino , Melanoma/metabolismo , Persona de Mediana Edad , Aceptación de la Atención de Salud , Receptor de Muerte Celular Programada 1/metabolismo , Estudios Retrospectivos , Estados UnidosRESUMEN
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.