Observational study to analyze patterns of treatment of breakthrough dyspnea in cancer patients in clinical practice

INTRODUCCIÓN: Siendo la disnea irruptiva un síntoma muy frecuente en los pacientes oncológicos, no existen recomendaciones precisas para su tratamiento. El objetivo principal del estudio fue analizar qué tratamientos se utilizan en la práctica clínica diaria para el manejo de la disnea irruptiva en pacientes con cáncer en España. Los objetivos secundarios fueron describir las características de los pacientes oncológicos con disnea irruptiva y los atributos de esta alteración. MÉTODOS: Pacientes oncológicos mayores de 18 años, con disnea irruptiva y estado funcional Karnofsky mayor o igual a 30, atendidos en servicios de oncología. Se recogió el historial de tratamientos para la disnea irruptiva y las características de esta patología, variables antropométricas, índice de disnea de Mahler, escala de Borg, escala Edmonton Symptoms Assessment Scale, satisfacción del paciente con el tratamiento actual de la disnea irruptiva. RESULTADOS: La edad media de los 149 pacientes incluidos fue de 66 años (intervalo de confianza 95%: 64,3 a 67,9), siendo mujeres el 35,6% (53). La intensidad media de la disnea irruptiva fue de 5,85 (intervalo de confianza 95%: 5,48 a 6,22 Borg). El 55,1% de los tratamientos de primera opción fueron los opioides, seguidos del oxígeno (17,3%). El 79,9% de los pacientes (119) fueron tratados en monoterapia. En los casos que presentaban disnea basal se administró oxígeno en mayor proporción 21,1% versus 7,4% (p = 0,07). Si la disnea era predecible se administró en mayor proporción opioides, 70,9% versus 44,4% (p = 0,01). CONCLUSIONES: Los opioides constituyen el tratamiento de primera línea de la disnea irruptiva en la práctica clínica habitual; sin embargo, el grado de evidencia científica que justifique su uso es escasa. Se necesita más información procedente de ensayos clínicos controlados en los que se evalúe la eficacia comparativa de diferentes tratamientos.INTRODUCTION: Although breakthrough dyspnea is very frequent in cancer patients, there are no precise recommendations for treating it. The main objective of this study was to analyze what treatments are used in clinical practice for the management of breakthrough dyspnea in cancer patients in Spain and the secondary objectives were to describe the characteristics of cancer patients with breakthrough dyspnea and the attributes of the disorder. METHODS: Cancer patients over 18 years of age, with breakthrough dyspnea and a Karnofsky performance score of ≥30, who were treated at departments of oncology in institutes across Spain were included in this cross-sectional observational study. The characteristics of breakthrough dyspnea, history of treatment, anthropometric variables, Mahler dyspnea index, Borg scale, Edmonton Symptoms Assessment Scale, and patient satisfaction with current breakthrough dyspnea treatment were assessed. RESULTS: The mean age of the 149 included patients was 66 years (95% confidence interval: 64.3 to 67.9), and 53 were females (35.6%). The mean breakthrough dyspnea intensity was 5.85 (95% confidence interval 5.48 to 6.22, Borg scale). A total of 55.1% of the first-choice treatments consisted of opioids, followed by oxygen (17.3%). A total of 119 patients (79.9%) received monotherapy for breakthrough dyspnea. Patients presenting with basal dyspnea received oxygen in a greater proportion of cases (21.1% vs 7.4%; p = 0.07). Patients with predictable dyspnea received a greater proportion of opioids (70.9% vs 44.4%; p = 0.01). CONCLUSIONS: Opioids constitute first-line therapy for breakthrough dyspnea in routine clinical practice, though the scientific evidence supporting their use is scarce. Further information derived from controlled clinical trials is needed regarding the comparative efficacy of the different treatments in order to justify their use.El presente estudio fue patrocinado por Kyowa Kirin Farmacéutica S. L. U., Madrid, España. El patrocinador no participó en el diseño del estudio, ni en la recolección, ni en el análisis de los datos. La decisión de publicar este trabajo fue iniciativa exclusiva de los autores. Asimismo, no hubo influencia en la preparación, revisión o aprobación del manuscrito

One-year efficacy and safety of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: KYONAL study

Cancer; Constipation; PainCàncer; Restrenyiment; DolorCáncer; Estreñimiento; DolorAbstract Objectives Naloxegol is a peripherally acting µ-opioid receptor antagonist (PAMORA) for treatment of opioid-induced constipation (OIC). The main objective was to analyse the long-term efficacy, quality of life (QOL) and safety of naloxegol in patients with cancer in a real-world study. Methods This one-year prospective study included patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky≥50 and OIC with inadequate response to treatment with laxative (s). All the patients received treatment with naloxegol according to clinical criteria. The main efficacy objectives were measured by the patient assessment of constipation QOL questionnaire (PAC-QOL), the PAC symptoms (PAC-SYM), the response rate at day 15, and months 1-3-6-12, and global QOL (EuroQoL-5D-5L). Results A total of 126 patients (58.7% males) with a mean age of 61.5 years (95% CI 59.4 to 63.7) were included. PAC-SYM and PAC-QOL total score and all their dimensions improved from baseline (p<0.0001). At 12 months, 77.8% of the patients were responders to naloxegol treatment. Global QOL was conserved from baseline. A total of 28 adverse reactions, mainly gastrointestinal were observed in 15.1% of the patients (19/126), being 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) appeared the first 15 days of treatment. Conclusion The results of this first long-term and real-world-data study in patients with cancer, showed the sustained efficacy and safety of naloxegol for the treatment of OIC in this group of patients.This study was sponsored by Kyowa Kirin Farmacéutica S.L., Spain. The funders participated in the design of the study and the drafting of the manuscript

Clinical and economic impact of ‘ROS1-testing’ strategy compared to a ‘no-ROS1-testing’ strategy in advanced NSCLC in Spain

Background Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain. Methods A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression-free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (euro 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty. Results A target population of 8755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to euro 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 euro/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis. Conclusions Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients

Clinical and economic impact of current ALK rearrangement testing in Spain compared with a hypothetical no-testing scenario

Background: Currently biomarkers play an essential role in diagnosis, treatment, and management of cancer. In non-small cell lung cancer (NSCLC) determination of biomarkers such as ALK, EGFR, ROS1 or PD-L1 is mandatory for an adequate treatment decision. The aim of this study is to determine the clinical and economic impact of current anaplastic lymphoma kinase testing scenario in Spain. Methods: A joint model, composed by decision-tree and Markov models, was developed to estimate the long-term health outcomes and costs of NSCLC patients, by comparing the current testing scenario for ALK in Spain vs a hypothetical no-testing. The current distribution of testing strategies for ALK determination and their sensitivity and specificity data were obtained from the literature. Treatment allocation based on the molecular testing result were defined by a panel of Spanish experts. To assess long-term effects of each treatment, 3-states Markov models were developed, where progression-free survival and overall survival curves were extrapolated using exponential models. Medical direct costs (expressed in €, 2019) were included. A lifetime horizon was used and a discount rate of 3% was applied for both costs and health effects. Several sensitivity analyses, both deterministic and probabilistic, were performed in order test the robustness of the analysis. Results: We estimated a target population of 7628 NSCLC patients, including those with non-squamous histology and those with squamous carcinomas who were never smokers. Over the lifetime horizon, the current ALK testing scenario produced additional 5060 and 3906 life-years and quality-adjusted life-years (QALY), respectively, compared with the no-testing scenario. Total direct costs were increased up to € 51,319,053 for testing scenario. The incremental cost-effectiveness ratio was 10,142 €/QALY. The sensitivity analyses carried out confirmed the robustness of the base-case results, being the treatment allocation and the test accuracy (sensitivity and specificity data) the key drivers of the model. Conclusions: ALK testing in advanced NSCLC patients, non-squamous and never-smoker squamous, provides more than 3000 QALYs in Spain over a lifetime horizon. Comparing this gain in health outcomes with the incremental costs, the resulting incremental cost-effectiveness ratio reinforces that testing non-squamous and never-smoker squamous NSCLC is a cost-effective strategy in Spain

Efficacy of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: a 3-month follow-up analysis

Objectives: Opioid-induced constipation (OIC) can affect up to 63% of all patients with cancer. The objectives of this study were to assess quality of life as well as efficacy and safety of naloxegol, in patients with cancer with OIC. Methods: An observational study was made of a cohort of patients with cancer and with OIC exhibiting an inadequate response to laxatives and treated with naloxegol. The sample consisted of adult outpatients with a Karnofsky performance status score ≥50. The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) and the Patient Assessment of Constipation Symptoms (PAC-SYM) were applied for 3 months. Results: A total of 126 patients (58.2% males) with a mean age of 61.3 years (range 34-89) were included. Clinically relevant improvements (>0.5 points) were recorded in the PAC-QOL and PAC-SYM questionnaires (p<0.0001) from 15 days of treatment. The number of days a week with complete spontaneous bowel movements increased significantly (p<0.0001) from 2.4 to 4.6 on day 15, 4.7 after 1 month and 5 after 3 months. Pain control significantly improved (p<0.0001) during follow-up. A total of 13.5% of the patients (17/126) presented some gastrointestinal adverse reaction, mostly of mild (62.5%) or moderate intensity (25%). Conclusions: Clinically relevant improvements in OIC-related quality of life, number of bowel movements and constipation-related symptoms were recorded as early as after 15 days of treatment with naloxegol in patients with cancer and OIC, with a good safety profile

Monitorización del tratamiento neoadyuvante en cáncer de recto localmente avanzado mediante ₑ⁸F-FDG PET: correlación predicitiva y pronóstica de la respuesta

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Radiología y Medicina Física, leída el 08-09-2014Depto. de Radiología, Rehabilitación y FisioterapiaFac. de MedicinaTRUEunpu

Proyecto adapta: adecuación del tratamiento en dolor irruptivo oncológico

ABSTRACT Introduction: Transmucosal fentanyl has specific properties which make it ideal for the treatment of breakthrough cancer pain (BTCP). Although there is a broad consensus for the administration of transmucosal fentanyl for BTCP in Spain, there is uncertainty as to the way oncologists adjust their prescription to the patient and what are the determinants of the choice of different pharmaceutical forms. Objectives: The main objective of this study was to analyze and prioritize the attributes that Spanish oncologists consider when assessing treatment options with transmucosal fentanyl in patients with BTCP. Methods: A Scientific Committee performed a classification of 14 relevant attributes in the prescription of transmucosal fentanyl for BTCP. Subsequently, a dossier of scientific evidence was generated comparing these 14 attributes among the different available transmucosal fentanyl formulations, which was shared with the panel of experts (115 Medical Oncologists). After a thorough review of the document, the participants carried out an online vote for the prioritization of the attributes. Results: Out of fourteen attributes analyzed, seven achieved a consensus of ≥ 50 % of the participants: the start of the analgesic action (84 %), the adequacy of the effect of fentanyl to the BTCP episode (72 %), the ease of use (58 %), the presence of mucositis (57 %), the ease of titration of the optimal dose (57%), and the variety of presentations and doses available (59 %). Conclusions: The most valued attributes were those related to the speed of action of the analgesic treatment and its adaptation to the BTCP profile, something to be expected given the spontaneous, unpredictable, and transitory nature of BTCP. As less valued attributes appear the risk of abuse or aberrant behavior and the presence of rhinitis for its administration, which indicates that the existence of these factors do not influence the choice of treatment for BTCP. These results will allow medical oncologists to know what attributes should be taken into account when customizing the patient's treatment of BTCP in order to improve the adequacy of rescue analgesia.RESUMEN Introducción: El fentanilo de administración transmucosa tiene características específicas que lo convierten en el fármaco adecuado para el tratamiento del dolor irruptivo oncológico (DIO). Aunque en España existe un amplio consenso sobre la idoneidad de la administración de fentanilo transmucoso para el DIO, es relevante conocer cómo los oncólogos adecuan su prescripción al paciente y cuáles son los factores determinantes de la elección de las diferentes formas farmacéuticas. Objetivos: El objetivo principal de este proyecto fue identificar y priorizar los atributos que los oncólogos médicos españoles tienen en cuenta cuando valoran las opciones de tratamiento con fentanilo transmucoso en pacientes con DIO. Métodos: Un comité científico realizó una tipificación de 14 atributos relevantes en la prescripción de fentanilo transmucoso para el DIO. Posteriormente se generó un dossier de evidencia científica comparando estos 14 atributos entre los distintos fentanilos transmucosos disponibles, que se compartió con el panel de expertos (115 oncólogos médicos). Tras una exhaustiva revisión del documento, los participantes realizaron una votación online de priorización de los atributos. Resultados: De catorce atributos analizados, siete consiguieron un consenso de ≥ 50 % de los participantes: el inicio de la acción analgésica (84 %), la adecuación del efecto del fentanilo al perfil del episodio de DIO (72 %), la facilidad de uso por los pacientes y cuidadores (69 %), la duración del efecto (58 %), la presencia de mucositis (57 %),la facilidad de titulación de la dosis óptima (57 %) y las presentaciones y dosis disponibles (59 %). Conclusiones: Los atributos más valorados fueron los relativos a la rapidez de acción del tratamiento analgésico y su adaptación al perfil del DIO, algo esperable dadas las características clínicas del episodio de DIO. Como atributos menos valorados aparecen el riesgo de abuso o conductas aberrantes y la presencia de rinitis para su administración, lo que indica que la existencia de estos factores no tiene tanta influencia en la elección del tratamiento para el abordaje del DIO. Estos resultados permitirán a los oncólogos médicos conocer qué atributos deben ser tenidos en cuenta a la hora de personalizar los tratamientos del paciente con DIO con el objetivo de mejorar la adecuación de la analgesia de rescate