A Real-world Study of Everolimus Plus Aromatase Inhibitor in Hormone Receptor-positive, HER2-negative Advanced Breast Cancer.

BACKGROUND/AIM: Everolimus in combination with exemestane was shown to offer benefit versus exemestane monotherapy in hormone receptor (HR)-positive, HER2-negative advanced breast cancer patients who progressed after aromatase inhibitor (AI) therapy. PATIENTS AND METHODS: The medical records of metastatic breast cancer patients, treated with everolimus, were retrospectively reviewed to generate real life safety and efficacy data. RESULTS: Sixty-eight percent of the patients had received chemotherapy (for early or metastatic disease) and 26% had received chemotherapy for metastatic disease. Among the 25 included patients, the most common adverse events were fatigue, neutropenia, epistaxis, stomatitis, and pneumonitis. Toxicity led to treatment discontinuation in 3 patients (12%). The median progression-free survival (PFS) was 7 months (95%CI=3.5-10.5). With a median follow-up of 73.3 months, the median overall survival was not reached. Twenty-five percent of the patients had received prior therapy with CDK4/6 inhibitors. Median PFS was significantly shorter in this subgroup (p=0.025). There was also a trend towards a longer PFS in patients with grade 3 breast cancer (p=0.085) and in patients receiving everolimus as first-line treatment (p=0.081). Some long responses were noted, with four patients exhibiting a PFS >5 years. CONCLUSION: These real-life data show that everolimus in combination with AI in patients with HER2-negative, HR-positive advanced breast cancer is an effective treatment with an acceptable toxicity profile.

Efficacy and safety of everolimus plus exemestane in patients with hormone receptor-positive, HER-2-negative advanced breast cancer: Results from the open-label, multicentre, non-interventional BRAWO study.

BRAWO, a real-world study, assessed the efficacy, quality of life (QoL) and safety of EVE + EXE in postmenopausal women with HR+/HER2- advanced breast cancer (ABC) in routine clinical practice. Postmenopausal women with HR+/HER2-ABC with recurrence or progression after a NSAI were included. Primary Observation parameters included the evaluation of the effectiveness of EVE + EXE. A multivariate-analysis using Cox proportional hazard model was built to identify predictors of progression. Overall, 2100 patients were enrolled (August 2012-December 2017); 2074 were evaluable for efficacy and safety analyses. Majority of patients (60.6%) received EVE + EXE as first (28.7%) or second-line (31.9%) therapy. Visceral metastases were present in 54.1% patients. Median progression-free survival (mPFS) reported as 6.6 months (95%CI: 6.3-7.0). Multivariate-analysis in a subset of patients (n = 1837) found higher body mass index (BMI) and non-visceral metastases to be independent predictors of favorable PFS. Patients with a BMI of 20 to <25 had a mPFS of 6.0 (95%CI: 5.4-6.4) and those with a BMI ≥30 had mPFS of 8.5 (95%CI: 6.9-9.9). 41.2% patients achieved stable disease and 7.3% partial response. No major changes were observed QoL; 86.4% patients received stomatitis prophylaxis and 41.4% experienced EVE related AEs of stomatitis, mainly low grade. AEs occurred in 91.2% of patients, of which stomatitis (42.6%) and fatigue (19.8%) were most frequent. The BRAWO study provides real-world evidence of efficacy and safety of EVE + EXE in patients with HR+, HER2- ABC. A high BMI and the absence of visceral metastases were independent predictors of PFS in this cohort of patients.

The effect of exemestane administration on the lipid profile in women: Meta-analysis of randomized controlled trials.

OBJECTIVE: Postmenopausal women are prone to develop cardiovascular disorders. In addition, cardiovascular risk in women can be influenced by the long-term prescription of drugs that lead to estrogen deprivation, e.g., aromatase inhibitors, and that can cause dyslipidemia. Little is known about the impact of exemestane, an aromatase inhibitor, on serum lipids' concentration in women. Hence, we conducted a meta-analysis of randomized controlled trials (RCTs) to assess the influence of this pharmacological agent on the lipid profile in women. METHODS: The Scopus, Web of Science, PubMed/Medline and EMBASE databases were searched by two surveyors for manuscripts published from the inception of these databases until April 3rd, 2023. No language restrictions were applied to the search. The random effects model was used to generate the combined results as weighted mean difference (WMD) and 95% confidence interval (CI). RESULTS: In total, 8 eligible RCTs were included in the meta-analysis. Overall results from the random effects model indicate that exemestane administration increases LDL-C (WMD: 4.42 mg/dL, 95 % CI: 0.44, 8.41, P = 0.02) and decreases HDL-C (WMD: -6.03 mg/dL, 95 % CI: -7.77, -4.29, P < 0.001) and TC (WMD: -5.40 mg/dL, 95 % CI: -9.95, -0.86, P = 0.02) levels, respectively. Moreover, exemestane prescription only lowered TG concentrations when it was administered for < 12 months (WMD: -14.60 mg/dL, 95 % CI: -23.57 to -5.62, P = 0.001). CONCLUSION: Currently available evidence suggests that the administration of exemestane in females increases LDL-C values and reduces HDL-C, TC, and, when prescribed for less than 12 months, TG concentrations.

Cortisol basal em asmáticos em uso de duas diferentes doses de propionato de fluticasona / Basal cortisol in asthmatics on two different doses of fluticasone propionate

OBJETIVOS: Avaliar os valores de cortisol basal em asmáticos persistentes em uso de propionato de fluticasona inalatório na dose de 200 ou 300 mcg/dia. MÉTODOS: O diagnóstico e a classificação da gravidade da asma basearam-se nas recomendações do Global Initiative for Asthma. Pacientes menores de 11 anos receberam fluticasona na dose de 200 mcg/dia, e aqueles com mais de 11 anos receberam 300 mcg/dia. Após 10 semanas de tratamento, a dosagem do cortisol foi realizada para avaliação da função adrenal. RESULTADOS: Foram avaliados 41 pacientes (65,9 por cento do sexo masculino) entre 6 e 18 anos. Não houve diferença significativa entre as médias de cortisol basal nos pacientes que receberam 200 mcg/dia de propionato de fluticasona (n = 13) e naqueles que receberam 300 mcg/dia (n = 28). CONCLUSÕES: Os achados mostram que doses baixas a moderadas de propionato de fluticasona não causam supressão adrenal.

OBJECTIVES: To evaluate basal plasma cortisol in persistent asthmatics on inhaled fluticasone propionate 200 mcg/day and 300 mcg/day. METHODS: Asthma diagnosis and classification was based on Global Initiative for Asthma recommendations. Patients aged 11 years old or less received fluticasone propionate 200 mcg/day and those older than 11 years received 300 mcg/day. After 10 weeks of treatment, plasma cortisol levels were monitored to evaluate the hypothalamic-pituitary-adrenal axis. RESULTS: Forty-one patients (65.9 percent males) aged 6 to 18 years old were evaluated. No statistical differences were found between plasma cortisol levels in patients who received 200 mcg/day (n = 13) and those who received 300 mcg/day (n = 28). CONCLUSIONS: Our results show that low and moderate doses of fluticasone propionate do not cause adrenal suppression.

Inhaled corticosteroids in the treatment of respiratory allergy: safety vs. efficacy

OBJETIVO: Revisar os mecanismos moleculares de ação, eficácia e potenciais efeitos adversos relacionados aos corticosteróides inalados (CEI) em crianças com asma persistente. FONTES DOS DADOS: Artigos de língua inglesa da base de dados MEDLINE. Foram empregados os termos: corticosteroids, inhaled corticosteroids, asthma, children, beclomethasone, fluticasone, budesonide, ciclesonide, growth, adrenal insufficiency, bone mineral density, oral candidiasis. Foram selecionados guias de tratamento, artigos de revisão, estudos controlados, meta-análises e revisões sistemáticas que avaliaram a eficácia e os eventos adversos do tratamento com CEI. SíNTESE DOS DADOS: Estudos in vivo e in vitro mostram que os CEI disponíveis apresentam diferentes características farmacocinéticas e farmacodinâmicas que lhes conferem diferentes potenciais de ação. Os CEI também diferem quanto aos efeitos adversos sistêmicos e locais. Salienta-se a biodisponibilidade desses produtos como essencial para determinar a incidência de efeitos colaterais. Em linhas gerais, os CEI são capazes de controlar a asma, reduzindo o número de exacerbações, atendimentos médicos, hospitalizações e a necessidade de pulsos de corticosteróides orais. Também se observa melhora da função pulmonar, sobretudo nos pacientes com asma de início recente. O efeito adversos mais documentado é a desaceleração transitória do ritmo de crescimento. CONCLUSÕES: Os CEI são o principal agente antiinflamatório utilizado no tratamento da asma persistente. Quando administrados em doses baixas, mostram-se seguros e efetivos. O monitoramento dos pacientes permite a detecção precoce de eventuais efeitos adversos associados aos CEI.

OBJECTIVE: Review the molecular mechanisms of action, efficacy, and potential side effects associated with inhaled corticosteroids (ICS) in children with persistent asthma. SOURCES: Articles in English from MEDLINE. The following terms were used: corticosteroids, inhaled corticosteroids, asthma, children, beclomethasone, fluticasone, budesonide, ciclesonide, growth, adrenal insufficiency, bone mineral density, and oral candidiasis. Treatment guidelines, review articles, controlled trials, meta-analyses, and systematic reviews evaluating the efficacy and the adverse events of treatment with ICS were selected. SUMMARY OF THE FINDINGS: In vivo and in vitro studies show that the available ICS have different pharmacokinetic and pharmacodynamic properties that result in different action potentials. ICS also differ as to the systemic and local side effects. The bioavailability of these products is essential in order to determine the incidence of side effects. In general, ICS are capable of controlling asthma, reducing the number of exacerbations, medical consultations, hospitalizations, and the need of oral corticosteroid (applications) bursts. Improvement can also be seen in pulmonary function, especially in patients with recent onset asthma. The most documented adverse effect is transitory decrease of growth rate. CONCLUSIONS: ICS are the main anti-inflammatory agent used to treat persistent asthma. When administered in low doses, they seem to be safe and effective. Patient monitoring allows for early detection of possible side effects associated with ICS.