Efficacy and safety of niraparib in platinum-sensitive recurrent ovarian cancer: retrospective observational study in a tertiary hospital.

BACKGROUND: Niraparib has been authorized for maintenance treatment of epithelial ovarian cancer after first-line treatment with platinum, in partial or complete response. OBJECTIVES: To evaluate the effectiveness and safety of maintenance niraparib in platinum-sensitive recurrent ovarian cancer (PSROC) patients in a tertiary hospital. MATERIALS AND METHODS: This retrospective observational unicentre study included women diagnosed with ovarian adenocarcinoma who received niraparib. Eligibility criteria encompassed women with PSROC, in response to platinum chemotherapy, and not previously treated with other PARPis. Data on demographics, comorbidities, BRCA mutation status, disease stage, treatment history and adverse events were recorded. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: A total of 33 patients were included, with a median age of 63.5 years. The majority of patients received niraparib at 200 mg/day based on Research on Adverse Drug Events and Report criteria. Median OS was 30 months (95% CI: 16.76-43.23), and median PFS was 8 months (95% CI: 2.48-13.52). Adverse effects were more frequent during the initial months of treatment, with most classified as CTCAE v5 grade 1-2. Dose reductions, interruption of treatment and discontinuations were observed due to haematologic toxicities primarily. CONCLUSION: This real-world study showed that maintenance niraparib in PSROC patients had effectiveness and safety profiles consistent with clinical trials and other observational studies. Median PFS and OS were comparable to previous reports, and most adverse events were manageable with dose modifications. The results support the use of niraparib as a maintenance therapy option in this patient population.

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.

Impact of Frailty on Outcomes of First-Line Pembrolizumab Monotherapy in a Real-World Population with Advanced Non-Small Cell Lung Cancer.

ICIs have been able to improve overall survival in advanced-stage lung cancer. The benefit of this therapy is limited in patients with poor ECOG PS. However, this scale is imprecise and can be influenced by different factors, such as frailty. Cancer patients have a high risk of frailty independently of age. In this observational, single-center, retrospective study, we investigated the effect of frailty on the effectiveness of pembrolizumab in first-line use in a cohort of 101 patients with metastatic NSCLC. Frailty was determined using a frailty score system developed by Sakakida et al. Univariate and multivariate analysis was performed to determine the prognostic role of frailty on OS and PFS. Median OS was significantly higher in patients with low frailty compared with intermediate and high frailty (23.8 vs. 7.0 and 1.8 months, respectively; p < 0.001). Median PFS was also significantly higher in patients with low frailty compared with intermediate and high frailty (10.5 vs. 3.9 and 1.6 months; p < 0.001, respectively). Frailty was the only variable that showed significant differences in OS and PFS. Multivariate analysis confirms frailty as an independent predictor of OS and PFS. Frailty assessment could help to select which patients are candidates for ICIs in NSCLC.

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.

Influence of Performance Status on the Effectiveness of Pembrolizumab Monotherapy in First-Line for Advanced Non-Small-Cell Lung Cancer: Results in a Real-World Population.

The KEYNOTE-024 clinical trial showed promising results for pembrolizumab in the first-line of treatment of advanced non-small-cell lung cancer (NSCLC). However, the profile of patients in real-world practice differs from those included in this clinical trial. Here, an observational single-center retrospective study was performed through a comparative analysis of clinical outcomes after pembrolizumab therapy according to the Eastern Cooperative Oncology Group Stage Performance Status (ECOG PS). Moreover, univariate and multivariate analyses were carried out to detect prognostic factors. In our cohort, 63.7% of patients had an ECOG PS of 0-1. Regarding response rate, 31.8% of patients had a partial response (PR), 19.3% had stable disease (SD) and 23.9% had progression disease. On the other hand, patients with ECOG PS ≥ 2 showed a significantly lower rate of PR and SD to pembrolizumab than patients with a PS of 0-1. The rate of response, median overall survival (OS) and progression-free survival (PFS) were significantly higher in patients with ECOG PS 0-1 than in those with ECOG PS ≥ 2. In the current study, we found ECOG PS as the only independent predictor of OS and PFS. Due to the ECOG PS scale being a subjective parameter, other tools are needed to identify treatment effectiveness to each patient.

Persistence to single-tablet regimen versus less-drug regimen in treatment experienced HIV-infected patients on antiretroviral therapy.

BACKGROUND: Decreased antiretroviral therapy persistence is associated with increased rates of virologic failure, development of antiretroviral resistance, and increased morbidity and mortality. Different therapeutic strategies, such as single-tablet regimens (STR) and less-drug regimens (LDR), have been developed in order to simplify antiretroviral therapy (ART) and increase persistence. OBJECTIVES: The primary objective was to compare antiretroviral persistence among patients receiving STRs and patients receiving LDRs. A secondary objective was to identify factors associated with non-persistence. METHODS: This was a retrospective study that included treatment- experienced HIV-infected patients who received ART based on STR or LDR. Baseline patient characteristics collected included demographic information, HIV risk transmission, substance abuse during the therapy, presence of psychiatric disorder and hepatitis B or C virus infection. Kaplan-Meier analysis and Log rank was utilized to compare persistence to STR and LDR. To identify independent predictors of non-persistence we developed a multivariate Cox regression analysis. RESULTS: A total of 244 patients were included, 176 with STR and 68 with LDR. 60 (34.1%) patients discontinued in the STR group and 13 (19.1%) in the LDR group. The Cox regression model showed that the only variable associated with higher risk of non-persistence was the substance abuse (HR = 2.59; p = 0.005). Adverse events were the main reason for ART discontinuation in the STR group and virologic failure in the LDR group. CONCLUSIONS: Persistence to STR and LDR seems to be similar in pretreated HIV-infected patients. Drug abuse was the only factor identified with a higher risk of non-persistence.

Objetivos: Analizar y comparar la persistencia entre las estrategias basadas en Single-Tablet Regimen (STR) y Less Drug Regimen (LDR) en pacientes VIH+. El objetivo secundario del estudio fue determinar factores predictores de persistencia. Material y métodos: Estudio observacional retrospectivo que incluyo los siguientes criterios: pacientes VIH+ con tratamiento antirretroviral (TAR) con un regimen basado en STR o LDR. Se recogieron variables demograficas, factores de riesgo de adquisicion, consumo de drogas, presencia de algun trastorno psiquiatrico y coinfeccion por el virus de la hepatitis B o C. Para comparar la persistencia entre ambas estrategias se realizo un analisis de supervivencia de Kaplan-Meir y se aplico el metodo de log-rank. Se realizo un analisis de regresion de Cox para identificar los factores predictores de persistencia. Resultados: Se incluyeron 244 pacientes, 176 con STR y 68 con LDR. El 34,1% (n = 60) de los pacientes que recibieron un regimen STR abandonaron y en el LDR el 19,1% (n = 13). Los efectos adversos fueron la principal causa de abandono del tratamiento en los pacientes que recibieron STR y el fallo virologico en el regimen LDR. La persistencia de las estrategias STR y LDR fue similar, no encontrandose diferencias estadisticamente significativas entre ambas. El consumo de drogas fue el unico factor predictivo asociado con una menor persistencia (HR = 2,59; p = 0,005). Conclusiones: La persistencia entre los regimenes STR y LDR fue similar, no detectandose diferencias significativas entre ambos. El consumo de drogas fue el unico factor independiente asociado con una menor persistencia del tratamiento antirretroviral.

Influence of pharmacotherapy complexity on compliance with the therapeutic objectives for HIV+ patients on antiretroviral treatment concomitant with therapy for dyslipidemia. INCOFAR Project.

OBJECTIVES: To analyze the relationship between pharmacotherapeutical complexity and compliance of therapeutic objectives in HIV+ patients on antiretroviral treatment and concomitant dyslipidemia therapy. MATERIALS AND METHODS: A retrospective observational study including HIV patients on stable antiretroviral treatment during the past 6 months, and dyslipidemia treatment between January and December, 2013. The complexity index was calculated with the tool developed by McDonald et al. Other variables analyzed were: age, gender, risk factor of HIV, smoking, alcoholism and drugs, psychiatric disorders, adherence to antiretroviral treatment and lipid lowering drugs, and clinical parameters (HIV viral load, CD4 count, plasma levels of total cholesterol, LDL, HDL, and triglycerides). In order to determine the predictive factors associated with the compliance of therapeutic objectives, univariate analysis was conducted through logistical regression, followed by a multivariate analysis. RESULTS: The study included 89 patients; 56.8% of them met the therapeutic objectives for dyslipidemia. The complexity index was significantly higher (p = 0.02) in those patients who did not reach the objective values (median 51.8 vs. 38.9). Adherence to lipid lowering treatment was significantly associated with compliance of the therapeutic objectives established for dyslipidemia treatment. A 67.0% of patients met the objectives for their antiretroviral treatment; however, the complexity index was not significantly higher (p = 0.06) in those patients who did not meet said objectives. CONCLUSIONS: Pharmacotherapeutical complexity represents a key factor in terms of achieving health objectives in HIV+ patients on treatment for dyslipidemia.

Objetivos: Analizar la relación entre complejidad farmacoterapéutica y cumplimiento de los objetivos terapéuticos en pacientes VIH+ con tratamiento antirretroviral activo y concomitante para la dislipemia. Material y métodos: Estudio observacional retrospectivo. Se seleccionaron pacientes con VIH en tratamiento antirretroviral estable durante los últimos 6 meses y tratamiento para la dislipemia entre enero-diciembre de 2013. Se calculó el índice de complejidad a través de la herramienta desarrollada por Mc Donald et al. Otras variables analizadas fueron: edad; sexo; factor de riesgo de adquisición del VIH; consumo de tabaco, alcohol y drogas; alteraciones psiquiátricas; adherencia al TAR y a fármacos hipolipemiantes y parámetros clínicos (carga viral VIH, recuento de CD4, niveles plasmáticos de colesterol total, LDL, HDL, y triglicéridos). Para determinar factores predictivos asociados con el cumplimiento de los objetivos terapéuticos se realizó un análisis univariante mediante regresión logística y, posteriormente, un análisis multivariante. Resultados: Se incluyeron 89 pacientes. El 56,8% cumplieron los objetivos terapéuticos para la dislipemia. El índice de complejidad fue significativamente mayor (p = 0,02) en pacientes que no alcanzaron los valores objetivo (mediana de 51,8 vs 38,9). La adherencia al tratamiento hipolipemiante fue relacionada de forma significativa con el cumplimiento de los objetivos terapéuticos establecidos para el tratamiento de la dislipemia. El 67,0% cumplieron los objetivos para el TAR, sin embargo el índice de complejidad no fue significativamente mayor (p = 0,06) en los pacientes que no cumplían objetivos. Conclusiones: La complejidad farmacoterapéutica constituye un factor clave en la consecución de los objetivos de salud en pacientes VIH+ que reciben tratamiento para la dislipemia.

Persistence profile to nucleos(t)ide analogue treatment for patients with chronic hepatitis B.

BACKGROUND: There are currently five approved nucleos(t)ide analogues (NUCs) for the management of chronic hepatitis B (CHB): lamivudine, adefovir dipivoxil, telbivudine, entecavir, and tenofovir disoproxil fumarate. OBJECTIVE: To determine the persistence rates among patients receiving NUCs for CHB at weeks 48, 96 and 144, compare them in these periods, and analyse the evolution of treatment persistence. METHODS: We conducted a retrospective study that included patients with CHB who initiated antiviral therapy and were attended to by the pharmaceutical care office between January 2002 and December 2011. Patients included in a clinical trial or patients who did not collect their medication personally were excluded. There were two different analyses: a comparative analysis of the persistence rates in three periods (weeks 1-48, weeks 48-96, and weeks 96-144); and a Kaplan-Meier analysis to evaluate the evolution of persistence. RESULTS: A total of 102 patients were included. Persistence rates were different in the three periods. They decreased during the course of the different periods, and the decline was more rapid between the first and second period. There were statistically significant differences in the non-persistence of the five drugs (p<0.005). Entecavir had the best profile of persistence, followed by tenofovir. CONCLUSIONS: This study showed that high genetic barrier drugs had a better profile of persistence in the initial treatment of patients with CHB. Data seem to suggest entecavir may offer better persistence rates than tenofovir, and the persistence rates for all five medications dropped in weeks 48-96.

[Design and validation of a satisfaction survey with pharmaceutical care received in hospital pharmacyconsultation]. / Diseño y validación de una encuesta de satisfacción con la atención farmacéutica recibida en las consultas de farmacia hospitalaria.

OBJECT: To design and to validate a questionnaire to assess satisfaction with pharmaceutical care (PC) received at the hospital pharmacy. METHODS: Multicentric study in five andalusian hospital in January 2013. A bibliography search was performed in PUBMED; MESH term; pharmaceutical services, patients satisfaction and questionnaire. Next, the questionnaire was produced by Delphi methodology with ten items and with the following variables; demographics, socials, pharrmacologicals and clinics which the patient was asked for the consequences of the PC in his treatment and illness and for the acceptance with the received service. The patient could answer between one= very insufficient and five= excellent. Before the validation phase questionnaire, a pilot phase was carried out. Descriptive analysis, Cronbach's alpha coefficient and intraclass correlation coefficient (ICC) were performed in both phases. Data analysis was conducted using the SPSS statistical software package release 20.0. RESULTS: In the pilot phase were included 21 questionnaires and 154 of them in validation phase (response index of 100%). In the last phase, 62% (N=96) of patients were men. More than 50% of patients answered "excelent" in all items of questionnaire in both phases. The Cronbach's alpha coefficient and ICC were 0.921 and 0.915 (95%IC: 0.847-0.961) and 0.916 and 0,910 (95%IC: 0.886-0.931) in pilot and validation phases, respectively. CONCLUSIONS: A high reliability instrument was designed and validated to evaluate the patient satisfaction with PC received at hospital pharmacy.

Objetivo: Diseñar y validar un cuestionario para valorar la satisfacción con la Atención Farmacéutica (AF) recibida en la farmacia hospitalaria. Métodos: Estudio multicéntrico en cinco hospitales andaluces. En enero 2013 se realizó una búsqueda bibliográfica en PUBMED; términos MESH pharmaceutical services, patients satisfaction and questionnaire. Seguidamente se elaboró el cuestionario, según metodología Delphi, formado por 10 ítems, con variables demográficas, sociales, farmacológicas y clínicas; donde se preguntaba al paciente sobre la repercusión de la AF en su tratamiento y enfermedad y sobre la conformidad con el servicio prestado. El paciente podía responder desde uno=muy deficiente a cinco=excelente. Se realizó una fase piloto previa a la fase de validación de los cuestionarios. Análisis descriptivos y la medida del valor del alfa de Cronbach y el coeficiente de correlación intraclase (CCI) se llevaron a cabo en ambas fases. Se utilizó el programa estadístico SPSS versión 20.0. Resultados: Se incluyeron 21 encuestas en la fase piloto y 154 en la fase de validación (índice de respuesta 100%). De esta última fase, el 62% (N=96) eran hombres. Más del 50% de los pacientes contestaron de forma "excelente" a todos los ítems de la encuesta en ambas fases. Los valores del alfa de Cronbach y CCI fueron 0.921 y 0.915 (IC95%: 0.847-0.961) y 0.916 y 0,910 (IC95%: 0.886-0.931) para fase piloto y validación, respectivamente. Conclusión: Se ha diseñado y validado un instrumento de alta fiabilidad para medir la satisfacción de los pacientes con la AF recibida en las consultas de farmacia hospitalaria.

Concurrent use of comedications reduces adherence to antiretroviral therapy among HIV-infected patients.

BACKGROUND: The use of highly active antiretroviral therapy has significantly reduced morbidity and mortality, thus increasing life expectancy of human immunodeficiency virus (HIV)-infected individuals, transforming HIV into a chronic disease. Accordingly, there has been an increase in the number of comorbidities concomitantly present in these individuals and also an increased use of comedications, which may negatively impact antiretroviral therapy adherence. These factors can affect adherence to antiretroviral therapy. The role of the HIV clinical pharmacist is essential to achieve therapeutic objectives and enhance adherence. OBJECTIVE: To determine the influence of the comorbidities and comedications on antiretroviral therapy adherence among HIV-infected patients receiving services from a clinical pharmacist. METHODS: We conducted a prospective observational study that included HIV-infected outpatients who attended the pharmaceutical care office of a hospital pharmacy service, which initiated antiretroviral treatment between January 2002, and December 2011. The variables analyzed in the study were demographics (sex and age), HIV transmission mode, and the following variables at the time of comedication collection: hepatitis C virus or hepatitis B virus coinfection, HIV plasma viral load (copies/mL) and CD4+ T-cell count (cells/µL), Centers for Disease Control and Prevention HIV classification, number of hospital admissions and emergency room visits, and antiretroviral therapy-related features (type at baseline, treatment-naïve status, and number of changes since starting antiretroviral therapy). For follow-up at 12 months, antiretroviral therapy adherence was measured through pharmacy dispensing records and the Morisky Medication Adherence Scale (MMAS). Patients were considered adherent if antiretroviral therapy adherence through dispensing records was greater than 90%, and the MMAS score was 4. Other variables were number of comorbidities and number of comedications for other chronic diseases (non-HIV drugs). According to the number of comorbidities, patients were categorized as having multiple chronic conditions (polypathology) if they had 2 or more chronic diseases. Polypharmacy was defined specifically as the use of 5 or more prescription medications in a medication regimen. In addition, a complexity therapeutic index of antiretroviral therapy was calculated for each patient. We determined the risk of drug-related problems using the tool Predictor Index. To identify independent predictors of adherence to antiretroviral therapy, we performed a univariate logistic regression. Afterward, those variables that showed statistical significance in the univariate analysis and those with P less than 0.25 were included in a multivariate model. The sample size was estimated by the Freeman equation. RESULTS: We included 594 patients in the study (80.1% men, median age 47 years). In the univariate analysis, the variables that showed statistically significant relationships with antiretroviral therapy adherence were HIV transmission mode, detectable viral load, CD4+ T-cell count, AIDS-defining condition, hospital admission, antiretroviral therapy-naïve treatment, type of antiretroviral therapy, high risk of drug-related problems, polypathology, and polypharmacy. Multivariate analysis showed that independent predictors of nonadherence to antiretroviral therapy were HIV transmission by intravenous drug use (OR = 0.56, 95% CI = 0.35-0.90), previous treatment with antiretroviral therapy (OR = 0.09, CI = 0.04-0.24), nontreatment changes (OR = 0.12, CI = 0.05-0.31), high risk of drug-related problems (OR = 0.38, CI = 0.23-0.63), and polypharmacy (OR = 0.36, CI = 0.21-0.61). The value of the Hosmer and Lemeshow test confirmed the validity of this model (P = 0.378). CONCLUSIONS: Recently, the number of HIV-infected patients with polypharmacy has been higher, increasing the risk of nonadherence. Furthermore, previous treatment with antiretroviral therapy, HIV transmission by intravenous drug use, and high risk of drug-related problems are also associated with lower adherence.