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.

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.

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.