Real-world data of atezolizumab in patients with previously treated locally advanced or metastatic urothelial bladder cancer.

BACKGROUND: Clinical trials of atezolizumab for locally advanced or metastatic urothelial bladder cancer (mUBC) report controversial efficacy data. Furthermore, real-world evidence about this use is limited. AIM: We aimed to evaluate the effectiveness of atezolizumab in a real-world population with mUBC, to explore effectiveness with regard to selected poor prognostic criteria such as performance status by Eastern Oncology Cooperative Group (ECOG), hemoglobin levels and liver metastases, and to determine the safety profile of atezolizumab. METHOD: Multicenter, retrospective real-world study including previously treated mUBC patients who received atezolizumab. The primary endpoint was overall survival (OS). Additionally, progression-free survival (PFS), best response reached and safety data were analyzed. A descriptive analysis was performed, while OS and PFS were estimated by Kaplan-Meier method. RESULTS: A total of 185 patients (84.9% men, median age 69 years) were included. Median PFS was 4.8 months [95% confidence interval (CI) 3.6-6.0], and median OS was 20.0 months (95% CI 11.8-28.5), with an objective response rate of 28.1%. OS was higher for patients with ECOG 0-1 versus 2-3 [24.5 months (95% CI 14.5-34.6) vs. 5.2 (95% CI 4.4-6.0), p = 0.004]; and for patients without liver metastases [25.4 months (95% CI 16.2-34.6) vs. 6.4 months (95% CI 4.0-8.1), p = 0.006]. Regarding hemoglobin levels, no survival differences were detected. Adverse events were registered in 55.1% of patients. CONCLUSION: In a real-world population with previously treated mUBC, atezolizumab seems to provide clinically relevant benefit, which is even higher for patients with ECOG 0-1 and without liver metastases, with an acceptable safety profile.

Effectiveness and safety of eribulin for human epidermal growth factor receptor 2 negative metastatic breast cancer in a real-world population.

BACKGROUND: Eribulin's clinical benefit remains unclear; so, studies analyzing its effectiveness in routine clinical practice are interesting. PATIENTS AND METHODS: This is a multicenter, retrospective study including patients with human epidermal growth factor receptor-2-negative metastatic breast cancer which assesses effectiveness and safety of eribulin. RESULTS: A total of 140 women were included, with a median age of 57 years. The median overall survival and progression-free survival were 8.8 (95% confidence interval: 6.1-11.4) and 2.8 months (95% confidence interval: 2.5-3.1), respectively. For patients with hormonal receptor expression, a significantly longer progression-free survival was observed: 3.4 (95%confidence interval: 2.3-4.5) versus triple negative: 2.0 (95%confidence interval: 1.7-2.3) months, p = 0.003. Also, those who had received capecitabine prior to eribulin had a higher median overall survival than those who had not received it (9.5 months, 95% confidence interval: 6.6-12.5 vs. 4.8 months, 95% confidence interval: 3.4-6.2; p = 0.001). When only triple-negative patients were included, median overall survival was 6.5 (95% confidence interval: 0.1-16.2) for those who had received previous capecitabine versus 4.3 (95% confidence interval: 2.8-5.8) months for patients who had not received it; p =0.006. The safety profile of eribulin was adequate. CONCLUSION: Effectiveness of eribulin in a real-life human epidermal growth factor receptor-2--negative population is lower than that observed in clinical trials. Its benefit seems to be higher in patients with hormonal receptor expression and patients who had received capecitabine prior to eribulin. The safety profile of eribulin is adequate.

Real world study of pertuzumab-trastuzumabchemotherapy versus trastuzumab-chemotherapy in neoadjuvant treatment of breast cancer.

OBJECTIVE: The primary objective of the study is to compare the  effectiveness of trastuzumab-chemotherapy with and without  pertuzumab. As a secondary objective, we seek to evaluate the cardiac  safety of the treatment. METHOD: Retrospective observational study including all patients treated with either pertuzumab-trastuzumab-chemotherapy (n = 10) or  trastuzumab-chemotherapy (n = 13) (January 2015-December 2018) in a specialty hospital, which met the criteria established by the  Commission Central for the Optimization and Harmonization of the  pharmacotherapy of the Andalusian Health Service for the use of  pertuzumab in neoadjuvance: HER2 positive tumor, negative hormonal  receptors, with high risk of relapse (tumor > 2 cm or lymph node  involvement). To assess effectiveness, the complete pathological  response was used. For cardiac safety, the decrease in left ventricular  ejection fraction greater than 10% was employed. RESULTS: Complete pathological response was superior in the  pertuzumab group (70.0% vs. 30.8%). Cardiac safety was similar in  both. CONCLUSIONS: For patients with HER2 positive tumors and negative hormonal receptors with high risk criteria that receive  pertuzumab, the complete pathological response is superior, with no  increase in cardiac toxicity.

Objetivo: El objetivo primario del estudio es comparar la efectividad trastuzumab-quimioterapia con y sin pertuzumab. Como  objetivo secundario se busca evaluar la seguridad cardiaca del  tratamiento.Método: Estudio observacional retrospectivo que incluyó todas las  pacientes tratadas con pertuzumab-trastuzumab-quimioterapia (n = 10) o trastuzumab-quimioterapia (n = 13) (enero 2015-diciembre 2018) en  un hospital de especialidades, que cumplían los criterios establecidos  por la Comisión Central para la Optimización y Armonización de la  farmacoterapia del Servicio Andaluz de Salud para uso de pertuzumab  en neoadyuvancia: tumor HER2 positivo, receptores hormonales  negativos, con alto riesgo de recaída (tumor > 2 cm o afectación  ganglionar). Para valorar la efectividad se utilizó la respuesta completa  patológica, y para la seguridad cardiaca, el descenso de la fracción de  eyección del ventrículo izquierdo superior al 10%.Resultados: La respuesta completa patológica fue superior en el grupo con pertuzumab (70,0% versus 30,8%). La seguridad cardiaca  fue similar en ambos.Conclusiones: Para las pacientes con tumores HER2 positivo y  receptores hormonales negativos con criterios de alto riesgo que reciben  pertuzumab, la respuesta completa patológica resulta superior,  sin observarse incremento de la toxicidad cardiaca.

Validation of the LESS-CHRON criteria: reliability study of a tool for deprescribing in patients with multimorbidity.

OBJECTIVE: The 'LESS-CHRON criteria' (List of Evidence-Based Deprescribing for Chronic Patients criteria) is a newly created tool with 27 criteria to guide deprescribing. It was developed using a Delphi methodology. Each criterion consists of drugs and their indications, conditions under which deprescribing would be considered, a health variable to be monitored after deprescribing and a follow-up period. The aim of our study was to evaluate the reliability of the LESS-CHRON criteria in a population of patients with multimorbidity to determine the possible usefulness of this tool in clinical practice. METHODS: We selected chronic patients with multimorbidity from an internal medicine unit who were older than 80 years old and were alive at the time of the study. To determine interobserver reliability, each professional (internist or hospital pharmacy specialist) applied the questionnaire under the same conditions and with the same resources. To determine intraobserver reliability, each health professional applied the tool at baseline and 2 months later. We measured interobserver and intraobserver reliability using the kappa coefficient. The proportion of overall agreement was also determined. RESULTS: We obtained a moderate overall kappa (ĸ=0.46, 95% CI 0.36 to 0.55) for interobserver reliability, and good (ĸ=0.65, 95% CI 0.57 to 0.78) and moderate (ĸ=0.59, 95% CI 0.49 to 0.74) values for intraobserver reliability for the internist and pharmacist, respectively. The proportion of overall agreement was very high: 92% (range: 62%-100%) for the interobserver, and 94% (80%-100%) and 93% (63%-100%) for the internist and pharmacist, respectively. CONCLUSIONS: The LESS-CHRON criteria shows early promise as a reliable method to help guide deprescribing in patients with multimorbidity. Further, more complete testing with a larger sample of prescribers is needed.

Prevalence of drug interactions in elderly patients with multimorbidity in primary care.

Background Drug interactions (DIs) are a significant cause of medication-related problems. The aging population, high chronic diseases prevalence and polypharmacy are closely associated factors. Aim of the review To study the prevalence, types and associated factors of DIs in multimorbidity patients of over 65 years of age in primary care. Methods Relevant studies on DI prevalence in this population were reviewed in PubMed, Cochrane Library and EMBASE (January 2000-December 2015). Independent variables (duration, target population, age, sex, mean of drugs and diseases, geographical localization, DI databases used and study designs) and dependent variables (prevalence, number of DIs per 100 patients and per patient, number of clinically-relevant DIs per 100 patients, most common DI and associated factors) were classified for each article. Results The search generated 749 articles and 46 duplicates were discarded. After reviewing, 10 articles were included. Seven studies were observational and 3 were quasi-experimental. Seven out of 10 used interaction databases. Only 2 studies described both actual and potential DIs. The prevalence of multimorbidity patients with DI ranged from 25.1 to 100% and the number of DIs per 100 patients was from 30 to 388.3. All the lower values correspond to the study conducted at the nursing home. This could be due to special care offered in these centres, where the medication is more controlled. The most frequent DIs were reported in five articles. However, these results could not be correlated since they were ranked using different methodologies. ACEIs, diuretics and NSAID were the most common therapeutic groups. Finally, 5 studies identified factors associated with the presence of potential DIs. The number of drugs and age were the most significant factors. Conclusions There is little evidence of prevalence of actual and potential DIs in elderly patients with multimorbidity in outpatient settings, showing widely heterogeneous results.

Effectiveness and safety of pemetrexed for non-small cell lung cancer in the Andalusian Public Health System.

OBJECTIVE: To evaluate effectiveness and safety profile of pemetrexed in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) when it´s used on real clinical practice in Andalusia (a Spanish region with 8.5 million inhabitants, 2014 census data). METHODS: An observational multicentre retrospective study was conducted. Adult patients with locally advanced/metastatic NSCLC who received pemetrexed in any hospital in the Andalusian Public Health System during the last term of 2011 were included. We collected patients´ baseline characteristics, diagnostic and treatment data, effectiveness variables (response to treatment with pemetrexed and overallsurvival) and main adverse reactions detected. RESULTS: 172 patients from 17 hospitals were included (77.33% were men), median age 63 years old (between 34 and 83). The predominant histology was adenocarcinoma (84.30%) and 85.20% were diagnosed of lung cancer with IV-stage. 78.49% had been smokers at some point in their lives. Median overall survival from the start of pemetrexed was 9 months (95%CI, 4.1-13.9). Progression of the disease was the most frequent response (33.14%), only one patient had complete response. Stable disease was associated with a higher probability of survival. Main adverse reactions detected were asthenia, haematological reactions, gastrointestinal reactions and dermal o mucous toxicity. No patients discontinued treatment for serious toxicity. CONCLUSIONS: Pemetrexed resulted quite effective in NSCLC when it was used on real clinical practice, with higher survival in non-squamous histology and patients with the best score of Eastern Cooperative Oncology Group scale. The toxicity profile was well tolerated. Prospective studies would be needed to confirm the effect of prognostic factors observed.

Objetivo: Evaluar la efectividad y el perfil de seguridad del pemetrexed en pacientes con cáncer de pulmón no microcítico (CPNM) localmente avanzado o metastásico en la práctica clínica real en Andalucía (una región española con 8,5 millones de habitantes según los datos del censo de 2014). Métodos: Se realizó un estudio retrospectivo multicéntrico observacional, incluyendo aquellos pacientes adultos con CPNM localmente avanzado/metastásico que hubiesen recibido pemetrexed en cualquier hospital del Sistema Sanitario Público de Andalucía durante el último trimestre de 2011. Se revisaron las características basales de los pacientes, los datos relativos al diagnóstico y al tratamiento, las variables de efectividad (en términos de respuesta al tratamiento con pemetrexed y supervivencia global) y las principales reacciones adversas detectadas. Resultados: Se incluyeron un total de 172 pacientes procedentes de 17 hospitales (77,33% hombres), con una mediana de edad de 63 años (rango: 34 y 83). La histología predominante fue el adenocarcinoma (84,30%) y el 85,20% fueron diagnosticados de cáncer de pulmón en estadio IV. El 78,49% habían sido fumadores en algún momento de sus vidas. La mediana de supervivencia global desde el inicio del pemetrexed fue de 9 meses (IC del 95%, 4,1-13,9). La progresión de la enfermedad fue la respuesta al tratamiento más frecuente (33,14%) y solo un paciente tuvo una respuesta completa. La presencia de enfermedad estable se asoció con una mayor probabilidad de supervivencia. Las principales reacciones adversas detectadas fueron astenia; reacciones hematológicas, gastrointestinales y dermatológicas o toxicidad mucosa. Ninguno de los pacientes interrumpió el tratamiento por toxicidad grave. Conclusiones: El pemetrexed resultó bastante efectivo en el CPNM cuando fue utilizado en la práctica clínica real, con una mayor supervivencia en histología no escamosa y en los pacientes con mejor puntuación en la escala Eastern Cooperative Oncology Group. El perfil de toxicidad fue bien tolerado. Serían necesarios estudios prospectivos para confirmar el efecto de los factores pronósticos observados.

Use of pemetrexed for non-small cell lung cancer in the Andalusian public health system.

The aim of this study is to determine the profile of the use of pemetrexed in metastatic or locally advanced NSCLC in Andalusia and its variation over 2 years (2010-2011). A prescription-indication observational retrospective multicenter study was conducted. Adult patients with locally advanced/metastatic NSCLC who received pemetrexed in any hospital in the Andalusian Public Health System during the first term of 2010 or the last term of 2011 were included. We collected patients' baseline characteristics, tumour histology and stage, pemetrexed indication and performance status at the start of treatment. In all, 107 and 170 patients (62 ± 11 years old) from 17 hospitals were included in 2010 and 2011, respectively. The predominant histology was adenocarcinoma (85%), 88% of patients had stage IV tumours and 52% Eastern Cooperative Oncology Group stage (ECOG) 1. Pemetrexed indications in 2010 and 2011 were: First line combined with platinum (28.97-37.64%); first line combined with platinum and maintenance with pemetrexed (24.30-28.82%); second line mono-therapy (12.15-7.65%) and maintenance (2.15-7.05%). Off-label use was detected in 22.43% (2010) and 18.84% (2011). In conclusion, pemetrexed combined with platinum is mainly used as first-line treatment in NSCLC patients with stage IV, adenocarcinoma histologic subtype and good performance status. Off-label use is high (especially in 2010). An adequate therapeutic positioning for pemetrexed based on effectiveness and safety analysis should be defined, so that NSCLC patients could be beneficiated with the most cost-effective chemotherapy treatment.

Systematic review of efficacy and safety of pemetrexed in non-small-cell-lung cancer.

INTRODUCTION: Lung cancer accounts for 20 % of cancer deaths in Spain. The most frequent subtype (87 %) is non-small cell lung cancer (NSCLC). Pemetrexed is a recently marketed drug added to NSCLC therapeutic arsenal. It seems to have become one of the most used options for the treatment of this condition over the last 3 years. AIM OF THE REVIEW: To evaluate the efficacy and safety of pemetrexed in NSCLC, in the different therapy lines. Method A systematic search of published literature was conducted using the main databases (MEDLINE, EMBASE, the Cochrane Library and the Center for Reviews and Dissemination) and subsequently a search of referenced literature was performed. We included clinical trials, meta-analyses and systematic reviews. The evaluation of the quality of the articles was performed by pairs using specific assessment scales, Critical Appraisal Skills Program (CASP) adapted for CASP Spain. Then we extracted data on efficacy and safety according to the treatment line assessed. RESULTS: We identified 277 references. Finally, nine clinical trials and a meta-analysis complied with inclusion criteria. In first-line induction, treatment with pemetrexed associated with a platinum was similar in terms of efficacy to other alternative chemotherapy regimens, except in patients with non-squamous histology, in whom survival was higher in the experimental group. In maintenance treatment, greater efficacy was seen with pemetrexed in patients with non-squamous histology. In second-line treatment, there were no significant differences in terms of efficacy and safety for pemetrexed treatment versus other chemotherapy options. The most frequent adverse reactions were: hematological, gastrointestinal and neurological. All were significantly less frequent with pemetrexed versus other alternative therapies, except for liver toxicity. CONCLUSIONS: Due to the high degree of uncertainty as to its efficacy in certain subgroups of patients, including conflicting data; to its recent incorporation, and therefore lack of safety data in the medium and long term, and the high budgetary impact of its incorporation into health systems, it seems reasonable to optimize its use, identifying those patients who may benefit most.

[Pharmacological treatment conciliation methodology in patients with multiple conditions]. / Metodología de conciliación del tratamiento farmacológico en pacientes pluripatológicos.

OBJECTIVE: To carry out a bibliographic review in order to identify the different methodologies used along the reconciliation process of drug therapy applicable to polypathological patients. DESIGN: We performed a literature review. Data sources The bibliographic review (February 2012) included the following databases: Pubmed, EMBASE, CINAHL, PsycINFO and Spanish Medical Index (IME). The different methodologies, identified on those databases, to measure the conciliation process in polypathological patients, or otherwise elderly patients or polypharmacy, were studied. Study selection Two hundred and seventy three articles were retrieved, of which 25 were selected. Data extraction Specifically: the level of care, the sources of information, the use of registration forms, the established time, the medical professional in charge and the registered variables such as errors of reconciliation. RESULTS: Most of studies selected when the patient was admitted into the hospital and after the hospital discharge of the patient. The main sources of information to be highlighted are: the interview and the medical history of the patient. An established time is not explicitly stated on most of them, nor the registration form is used. The main professional in charge is the clinical pharmacologist. Apart from the home medication, the habits of self-medication and phytotherapy are also identified. The common errors of reconciliation vary from the omission of drugs to different forms of interaction with other medicinal products (drugs interactions). CONCLUSIONS: There is a large heterogeneity of methodologies used for reconciliation. There is not any work done on the specific figure of the polypathological patient, which precisely requires a standardized methodology due to its complexity and its susceptibility to errors of reconciliation.

[Suitability of pharmacological treatment in patients with multiple chronic conditions]. / Adecuación del tratamiento farmacológico en pacientes pluripatológicos.

OBJECTIVE: To identify tools for measuring the appropriateness of drug therapy useful in patients with multiple chronic conditions. DESIGN: We performed a literature review. DATA SOURCES: The following database were consulted (December 2009): Pubmed, EMBASE, CINAHL, PsycINFO and Spanish Medical Index (IME) to detect tools for measuring the appropriateness of treatment in patients with multiple chronic conditions, or otherwise elderly or polypharmacy. STUDY SELECTION: Studies were identified both qualitative and quantitative methodology, both theoretical and field work, both original and revised work and included work from all areas of the health system. 108 articles were retrieved, of which we selected 59. The consultation of their references include 20 jobs allowed, resulting in a total of 59 articles. DATA EXTRACTION: Of all the tools identified, the researchers performed a selection of those with possible utility for classified PP. The articles were classified into implicit and explicit methods and the characteristics of the field works were tabulated. RESULTS: We identified two implicit methods (MAI and Hamdy) and 6 explicit methods (Beers criteria, IPET, STOPP/START, ACOVE, CRIME and NORGEP). None was specific to patients with multiple chronic conditions. The questionnaire MAI, the Beers criteria and its modifications are most often used in literature. The advantages of explicit criteria means that many of them have been developed recently. CONCLUSION: There are several tools to measure the appropriateness and none of them has been designed for a population of patients with multiple chronic conditions yet, which by its nature requires a specific approach spreads.