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

Phase II clinical trial of nab-paclitaxel plus gemcitabine in elderly patients with previously untreated locally advanced or metastatic pancreatic adenocarcinoma: the BIBABRAX study

[Purpose] To evaluate the health-related quality of life (HRQoL), global health status (GHS), and deterioration-free survival of an elderly population (> 70 years) with unresectable locally advanced (LAPC) or metastatic pancreatic cancer (mPC) treated with nab-paclitaxel in combination with gemcitabine.[Methods] In this open-label, single-arm, multicenter, phase II trial, patients received 4-week cycles of intravenous (i.v.) nab-paclitaxel at a dose of 125 mg/m2, followed by i.v. injections of gemcitabine at a dose of 1000 mg/m2 on days 1, 8 and 15 until disease progression or unacceptable toxicity was observed. The primary outcome was the HRQoL (deterioration-free rate at 3 months as evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30.[Results] Eighty patients (median age: 74.6 years) were enrolled (56 with mPC, 24 with LAPC). The percentage of patients who had not experienced deterioration at 3 months was 54.3% (95% CI 41.6–67.0%). The median (interquartile range) time until definite deterioration was 1.6 (1.1–3.7) months. The objective response rate and clinical benefit rate were achieved by 11 (13.8%, 95% CI 6.2–21.3%) and 54 patients (67.5%, 95% CI 57.2–77.8%), respectively. The median overall survival was 9.2 months (95% CI 6.9–11.5), and the median progression-free survival was 7.2 months (95% CI 5.8–8.5). Only fatigue and neutropenia demonstrated a grade 3–4 toxicity incidence > 20%.[Conclusions] Our study confirms the clinical benefit of the combination of nab-paclitaxel and gemcitabine in an elderly population with pancreatic cancer in terms of improved survival and clinical response. However, we were unable to confirm a benefit in terms of quality-of-life.The BIBABRAX study was funded by Celgene. Medical writing assistance in the preparation of this paper was provided by Apices with financial support from Celgene.Peer reviewe

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

Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2– advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial

Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone.Methods: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.Results: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade >= 3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade >= 3 neutropenia and anemia. Efficacy results were consistent with the global study.Conclusions: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2-ABC, including populations of interest (NCT02941926).Trial registration: ClinicalTrials.gov NCT0294192

The importance of early identification of infusion-related reactions to monoclonal antibodies

Monoclonal antibodies constitute important and useful tools in clinical practice and biotechnology for diagnosing and treating infectious, inflammatory, immunological and neoplastic diseases. This article reviews evidence on the different acute adverse effects of monoclonal antibodies, specifically infusion-related reactions (IRRs), and on the measures that should be taken before and during crises. A literature search using key terms relating to IRRs produced by monoclonal antibodies was undertaken to generate a comprehensive narrative review of the information available. Immunomodulatory monoclonal antibodies may produce IRRs and hypersensitivity-related reactions. Strategies to avoid or minimize the appearance of IRRs depend on the monoclonal antibody and type of patient and reaction (pre-medication, slowing infusion rates, infusion interruption or desensitization, etc.). Considering the great number of available monoclonal antibodies in current practice and those which will soon be authorized, it is mandatory to have clear guidelines that can give support to practitioners and nurses to help them respond quickly and safely to the different IRRs related to the use of these therapeutic drugs.This work was partially financed by a grant of the Regional Goverment of Extremadura; European Regional Development Fund (FEDER; IB18101).peerReviewe

Diseño de un módulo de prácticas interdisciplinares en paleontología aplicada

El proyecto de redes ha visto el desarrollo y el diseño de prácticas de carácter interdisciplinar (esquema de trabajo colaborativo entre alumnos y profesores) en el ámbito de la paleontología aplicada en estudios de Grado y de Máster, involucrando tanto el área de conocimiento de paleontología como a la de estratigrafía del Departamento de Ciencias de la Tierra y del Medio Ambiente de la Universidad de Alicante. En la acción educativa propuesta se ha planteado una coordinación entre las áreas de paleontología y estratigrafía para diseñar y llevar a cabo de forma conjunta actividades de campo y de laboratorio. Por ello, se elaboraron actividades de carácter interdisciplinar que los alumnos han ido desarrollando durante las salidas de campo y las sesiones de laboratorio y se realizó un muestreo para el desarrollo de las actividades de laboratorio compartidas entre las asignaturas. Al finalizar cada una de las asignaturas involucradas, se propuso a los alumnos una entrevista sobre la experiencia llevada a cabo, destacando aspectos positivos, elementos a mejorar y dificultades encontradas. Los resultados de las entrevistas y de la puesta en común en grupos de debate se utilizarán para la puesta en marcha de la acción educativa en los siguientes cursos académicos

Diseño de un módulo de prácticas interdisciplinares en paleontología aplicada

El proyecto de redes ha visto el desarrollo y el diseño de prácticas de carácter interdisciplinar (esquema de trabajo colaborativo entre alumnos y profesores) en el ámbito de la paleontología aplicada en estudios de Grado y de Máster, involucrando tanto el área de conocimiento de paleontología como a la de estratigrafía del Departamento de Ciencias de la Tierra y del Medio Ambiente de la Universidad de Alicante. En la acción educativa propuesta se ha planteado una coordinación entre las áreas de paleontología y estratigrafía para diseñar y llevar a cabo de forma conjunta actividades de campo y de laboratorio. Por ello, se elaboraron actividades de carácter interdisciplinar que los alumnos han ido desarrollando durante las salidas de campo y las sesiones de laboratorio y se realizó un muestreo para el desarrollo de las actividades de laboratorio compartidas entre las asignaturas. Al finalizar cada una de las asignaturas involucradas, se propuso a los alumnos una entrevista sobre la experiencia llevada a cabo, destacando aspectos positivos, elementos a mejorar y dificultades encontradas. Los resultados de las entrevistas y de la puesta en común en grupos de debate se utilizarán para la puesta en marcha de la acción educativa en los siguientes cursos académicos

Patient-Reported Outcomes in Patients With PIK3CA-Mutated Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer From SOLAR-1.

PurposeIn the phase III SOLAR-1 trial (NCT02437318), the PI3Kα-selective inhibitor and degrader alpelisib significantly improved median progression-free survival when added to fulvestrant in patients with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. We assessed health-related quality of life using patient-reported outcome measures in these patients.Materials and methodsIn the PIK3CA-mutant cohort, 341 patients were randomly assigned 1:1 to receive alpelisib 300 mg daily or placebo plus fulvestrant 500 mg on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day cycles. Patient-reported outcomes were evaluated with the European Organisation for Research and Treatment of Cancer QoL of Cancer Patients and Brief Pain Inventory-Short Form questionnaires. Changes from baseline and time to 10% deterioration were analyzed using repeated measurement models and Cox models, respectively.ResultsGlobal Health Status/QoL and functional status were maintained from baseline (mean changes &lt; 10 points) in the alpelisib (overall change from baseline [95% CI], -3.50 [-8.02 to 1.02]) and placebo arms (overall change from baseline [95% CI], 0.27 [-4.48 to 5.02]). Overall treatment effect in Global Health Status/QoL was not significantly different between arms (-3.77; 95% CI, -8.35 to 0.80; P = .101). Time to 10% deterioration for Global Health Status/QoL was similar between arms (hazard ratio, 1.03; 95% CI, 0.72 to 1.48). Compared with placebo, deterioration in social functioning and in diarrhea, appetite loss, nausea or vomiting, and fatigue symptom subscales occurred with alpelisib. Numerical improvement in Worst Pain was observed with alpelisib versus placebo (42% v 32%, week 24; P = .090).ConclusionIn SOLAR-1, there was no statistical difference in deterioration of Global Health Status/QoL between arms, whereas symptom subscales favored placebo for diarrhea, appetite loss, nausea or vomiting, and fatigue, known side effects of alpelisib. Treatment decisions must consider efficacy and tolerability; taken with clinical efficacy, these results support the benefit-risk profile of alpelisib in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative PIK3CA-mutated advanced breast cancer