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

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 < 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

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

International audienc