The efficacy of placebo for the treatment of cancer-related fatigue: a systematic review and meta-analysis.

PURPOSE: Cancer-related fatigue (CRF) is a common symptom among patients with cancer. The efficacy of placebo, however, was never the main objective of any meta-analysis. Predicting the efficacy of placebo may facilitate researchers in designing future clinical trials for the treatment of CRF. METHODS: We performed a systematic review searching for prospective clinical trials comparing any treatment versus placebo for the treatment of CRF. We included studies that enrolled patients with any primary site of neoplasia and any stage of cancer. We excluded all studies that assessed fatigue related to any treatment. The primary endpoint of this study is the mean effect of placebo on fatigue according to the Functional Assessment of Chronic Illness (FACIT-F) and Brief Fatigue Inventory (BFI) scales. The secondary endpoint was the proportion of patients who reported improvement in fatigue (response rate). RESULTS: We found 520 studies, and 29 studies with 3758 participants were included in the meta-analysis. Placebo had a mean effect of + 4.88 (95%CI + 2.45 to + 7.29) using the FACIT-F scale, although it was statistically worse than the interventions studied (p = 0.005). Using the BFI scale, placebo had an average effect of + 0.64 (95%CI + 0.02 to + 1.30), although it was also worse than the other interventions studied (p = 0.002). In terms of the response rate, 29% (95%CI 25-32%) of patients taking a placebo reported a significant improvement in CRF compared with 36% of patients treated with other interventions (p = 0.030). CONCLUSIONS: Placebo treatments had a significant effect on CRF, and predicting these effects may help design future studies for CRF.

Potential life years not saved due to lack of access to anti-EGFR tyrosine kinase inhibitors for lung cancer treatment in the Brazilian public healthcare system: Budget impact and strategies to improve access. A pharmacoeconomic study

ABSTRACT BACKGROUND: Lung cancer is the fourth most common cancer in Brazil. In the 2000s, better understanding of molecular pathways led to development of epidermal growth factor receptor (EGFR)-targeted treatments that have improved outcomes. However, these treatments are unavailable in most Brazilian public healthcare services (Sistema Único de Saúde, SUS). OBJECTIVE: To assess the potential number of years of life not saved, the budget impact of the treatment and strategies to improve access. DESIGN AND SETTING: Pharmacoeconomic study assessing the potential societal and economic impact of adopting EGFR-targeted therapy within SUS. METHODS: We estimated the number of cases eligible for treatment, using epidemiological data from the National Cancer Institute. We used data from a single meta-analysis and from the Lung Cancer Mutation Consortium (LCMC) study as the basis for assessing differences in patients' survival between use of targeted therapy and use of chemotherapy. The costs of targeted treatment were based on the national reference and were compared with the amount reimbursed for chemotherapy through SUS. RESULTS: There was no life-year gain with EGFR-targeted therapy in the single meta-analysis (hazard ratio, HR, 1.01). The LCMC showed that 1,556 potential life-years were not saved annually. We estimated that the annual budget impact was 125 million Brazilian reais (BRL) with erlotinib, 48 million BRL with gefitinib and 52 million BRL with afatinib. Their incremental costs over chemotherapy per life-year saved were 80,329 BRL, 31,011 BRL and 33,225 BRL, respectively. A drug acquisition discount may decrease the budget impact by 30% (with a 20% discount). A fixed cost of 1,000 BRL may decrease the budget impact by 95%. CONCLUSION: Reducing drug acquisition costs may improve access to EGFR-targeted therapy for lung cancer.

Cost-effectiveness analysis of abiraterone, docetaxel or placebo plus androgen deprivation therapy for hormone-sensitive advanced prostate cancer.

OBJECTIVE: To evaluate the cost-effectiveness of the addition of chemotherapy or abiraterone to androgen deprivation. METHODS: We developed an analytical model to determine the cost-effectiveness of the addition of docetaxel or abiraterone versus androgen deprivation therapy alone. Direct and indirect costs were included in the model. The effects were expressed in Quality-Adjusted Life Years adjusted for side effects. RESULTS: Compared to androgen deprivation therapy alone, the addition of chemotherapy and of abiraterone generated 0.492 and 0.999, respectively, in Quality-Adjusted Life Years. Abiraterone led to a Quality-Adjusted Life Years gain of 0.506 compared to docetaxel. The incremental costs per Quality-Adjusted Life Years were R$ 133.649,22 for docetaxel, R$ 330.828,70 for abiraterone and R$ 571.379,42 for abiraterone compared to docetaxel, respectively. CONCLUSION: The addition of chemotherapy to androgen deprivation therapy is more cost-effective than the addition of abiraterone to androgen deprivation therapy. However, discounts on abiraterone cost might improve cost-effectiveness.

Potential life years not saved due to lack of access to anti-EGFR tyrosine kinase inhibitors for lung cancer treatment in the Brazilian public healthcare system: Budget impact and strategies to improve access. A pharmacoeconomic study.

BACKGROUND: Lung cancer is the fourth most common cancer in Brazil. In the 2000s, better understanding of molecular pathways led to development of epidermal growth factor receptor (EGFR)-targeted treatments that have improved outcomes. However, these treatments are unavailable in most Brazilian public healthcare services (Sistema Único de Saúde, SUS). OBJECTIVE: To assess the potential number of years of life not saved, the budget impact of the treatment and strategies to improve access. DESIGN AND SETTING: Pharmacoeconomic study assessing the potential societal and economic impact of adopting EGFR-targeted therapy within SUS. METHODS: We estimated the number of cases eligible for treatment, using epidemiological data from the National Cancer Institute. We used data from a single meta-analysis and from the Lung Cancer Mutation Consortium (LCMC) study as the basis for assessing differences in patients' survival between use of targeted therapy and use of chemotherapy. The costs of targeted treatment were based on the national reference and were compared with the amount reimbursed for chemotherapy through SUS. RESULTS: There was no life-year gain with EGFR-targeted therapy in the single meta-analysis (hazard ratio, HR, 1.01). The LCMC showed that 1,556 potential life-years were not saved annually. We estimated that the annual budget impact was 125 million Brazilian reais (BRL) with erlotinib, 48 million BRL with gefitinib and 52 million BRL with afatinib. Their incremental costs over chemotherapy per life-year saved were 80,329 BRL, 31,011 BRL and 33,225 BRL, respectively. A drug acquisition discount may decrease the budget impact by 30% (with a 20% discount). A fixed cost of 1,000 BRL may decrease the budget impact by 95%. CONCLUSION: Reducing drug acquisition costs may improve access to EGFR-targeted therapy for lung cancer.

Cost-effectiveness analysis of abiraterone, docetaxel or placebo plus androgen deprivation therapy for hormone-sensitive advanced prostate cancer / Análise de custo-efetividade da adição de abiraterona ou quimioterapia ao tratamento do câncer de próstata metastático hormônio-sensível

ABSTRACT Objective To evaluate the cost-effectiveness of the addition of chemotherapy or abiraterone to androgen deprivation. Methods We developed an analytical model to determine the cost-effectiveness of the addition of docetaxel or abiraterone versus androgen deprivation therapy alone. Direct and indirect costs were included in the model. The effects were expressed in Quality-Adjusted Life Years adjusted for side effects. Results Compared to androgen deprivation therapy alone, the addition of chemotherapy and of abiraterone generated 0.492 and 0.999, respectively, in Quality-Adjusted Life Years. Abiraterone led to a Quality-Adjusted Life Years gain of 0.506 compared to docetaxel. The incremental costs per Quality-Adjusted Life Years were R$ 133.649,22 for docetaxel, R$ 330.828,70 for abiraterone and R$ 571.379,42 for abiraterone compared to docetaxel, respectively. Conclusion The addition of chemotherapy to androgen deprivation therapy is more cost-effective than the addition of abiraterone to androgen deprivation therapy. However, discounts on abiraterone cost might improve cost-effectiveness.

RESUMO Objetivo Avaliar a relação custo-efetividade da adição de quimioterapia ou abiraterona à terapia de privação hormonal. Métodos Um modelo analítico foi desenvolvido para determinar a relação custo-efetividade da adição de docetaxel ou abiraterona comparada à terapia de privação hormonal isolada. Custos diretos e indiretos foram incluídos no modelo. Os efeitos foram expressos em Anos de Vida Ajustados para Qualidade corrigidos pelos efeitos colaterais de cada terapia. Resultados A adição de quimioterapia e de abiraterona à terapia de privação hormonal aumentou os Anos de Vida Ajustados para Qualidade em 0,492 e 0,999, respectivamente, em comparação à terapia de privação hormonal isolada. A abiraterona promoveu ganho de Anos de Vida Ajustados para Qualidade de 0,506 em relação ao docetaxel. O custo incremental por Anos de Vida Ajustados para Qualidade foi R$ 133.649,22 para o docetaxel, R$ 330.828,70 para a abiraterona e R$ 571.379,42 para a abiraterona comparada ao docetaxel. Conclusão A adição de quimioterapia à terapia de privação hormonal é mais custo-efetiva que a adição de abiraterona à terapia de privação hormonal. Contudo, descontos no custo da abiraterona poderiam tornar esse tratamento mais custo-efetivo.

A paradigm shift for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer: a review of CDK inhibitors.

In the last 3 years, a novel class of targeted therapy has been approved for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. There are currently three approved agents, which are oral cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. All of the approved drugs exhibit progression-free survival benefit when compared to standard of care and generally have less adverse events compared to traditional chemotherapeutic options. The treatment of HR+/HER2- advanced breast cancer is a continuously evolving landscape, and the addition of CDK4/6 inhibitors is the newest mechanism for treatment. In this review, we summarize all available data, highlight the unanswered questions, and discuss pharmacological differences between each CDK4/6 inhibitor.

Immune checkpoint inhibitors for advanced non-small cell lung cancer: emerging sequencing for new treatment targets.

Lung cancer is the leading cause of cancer-related deaths in the world. Immune checkpoint inhibitors (ICI) stimulate cytotoxic lymphocyte activity against tumour cells. These agents are available for the treatment of non-small cell lung cancer (NSCLC) after failure of platinum-based therapy. One recent study has demonstrated that ICI monotherapy was superior to platinum-based chemotherapy for first-line treatment. Nevertheless, this benefit was only for a minority of the population (30%) whose tumour programmed death receptor ligand-1 (PD-L1) expression was above 50%. Therefore, several strategies are under investigation. One option for patients with PD-L1 expression lower than 50% may be the combination of ICI with platinum-based chemotherapy or with ICIs against different targets. However, all of these combinations are at an early stage of investigation and may be very expensive or toxic, producing several harmful adverse events.

Cost effectiveness of chemohormonal therapy in patients with metastatic hormone-sensitive and non-metastatic high-risk prostate cancer.

OBJECTIVE: To assess the cost-effectiveness of chemohormonal therapy in patients with metastatic hormone-sensitive and non-metastatic high-risk prostate cancer. METHODS: An analytical decision model was developed to determine the cost-effectiveness of chemohormonal therapy versus androgen deprivation therapy alone in patients with metastatic hormone-sensitive prostate cancer and patients with non-metastatic high-risk prostate cancer. The cost-effectiveness in metastatic patients with a high-volume disease was assessed separately. The model used data from randomized clinical trials and drug acquisition costs in Brazil. In addition, the costs of post-progression therapies have been included in this model. The benefits to health are expressed as the quality-adjusted life-years, and the incremental cost-effectiveness ratios were calculated. RESULTS: Chemohormonal therapy may be associated with improved quality-adjusted life-years for all patient. The improvement was more than six times greater for patients with high-volume metastatic disease. In these patients, the incremental cost-effectiveness ratios were up to 74% lower than the incremental cost-effectiveness ratios of patients with non-metastatic disease. CONCLUSION: Chemohormonal therapy has been more cost-effective in patients with high-volume metastatic disease.

Cost effectiveness of chemohormonal therapy in patients with metastatic hormone-sensitive and non-metastatic high-risk prostate cancer / Custo-efetividade da adição de quimioterapia ao tratamento hormonal do câncer de próstata metastático sensível a hormônio ou localizado de alto risco

ABSTRACT Objective To assess the cost-effectiveness of chemohormonal therapy in patients with metastatic hormone-sensitive and non-metastatic high-risk prostate cancer. Methods An analytical decision model was developed to determine the cost-effectiveness of chemohormonal therapy versus androgen deprivation therapy alone in patients with metastatic hormone-sensitive prostate cancer and patients with non-metastatic high-risk prostate cancer. The cost-effectiveness in metastatic patients with a high-volume disease was assessed separately. The model used data from randomized clinical trials and drug acquisition costs in Brazil. In addition, the costs of post-progression therapies have been included in this model. The benefits to health are expressed as the quality-adjusted life-years, and the incremental cost-effectiveness ratios were calculated. Results Chemohormonal therapy may be associated with improved quality-adjusted life-years for all patient. The improvement was more than six times greater for patients with high-volume metastatic disease. In these patients, the incremental cost-effectiveness ratios were up to 74% lower than the incremental cost-effectiveness ratios of patients with non-metastatic disease. Conclusion Chemohormonal therapy has been more cost-effective in patients with high-volume metastatic disease.

RESUMO Objetivo Avaliar a relação custo-efetividade da adição de quimioterapia hormonal em pacientes com câncer de próstata metastático sensível a hormônio ou localizado de alto risco. Métodos Um modelo de decisão analítico foi desenvolvido para determinar o custo-efetividade da adição de quimioterapia versus a monoterapia de privação de andrógeno para pacientes com câncer de próstata metastático hormônio-sensível e pacientes de alto risco com câncer de próstata não metastático. O custo-efetividade em pacientes metastáticos com um alto volume da doença foi verificado isoladamente. Os dados do modelo foram obtidos de ensaios clínicos randomizados utilizando custos de aquisição de medicamentos no Brasil. Os custos de terapias pós-progressão também foram incluídos no modelo. Os efeitos foram expressos em anos de vida ajustados por qualidade, e foram calculadas as razões de custo-efetividade incremental. Resultados A adição de quimioterapia levou a um ganho de anos de vida ajustados por qualidade para todos os doentes. Este incremento foi seis vezes maior para os pacientes com doença metastática de alto volume. Nestes pacientes, as taxas do custo incremental por anos de vida ajustados por qualidade foram até 74% mais baixos do que o aumento das taxas dos pacientes com doença não metastática. Conclusão A adição de quimioterapia foi mais custo-efetiva para pacientes com doença metastática de alto volume.

[Geographical distribution of leptospirosis in Aracaju, State of Sergipe from 2001 to 2007]. / Espacialização da leptospirose em Aracaju, Estado de Sergipe, no período de 2001 a 2007.

INTRODUCTION: Leptospirosis, a disease caused by pathogenic spirochetes of the genus Leptospira, is one of the most widespread zoonoses in the world and is considered an important public health problem. This paper aims to describe the spatial pattern of leptospirosis in the City of Aracaju from 2001 to 2007 in an effort to identify areas at risk for leptospirosis. METHODS: We used the ratio of Kernel, which represents the ratio between two surfaces, to visualize the surface of disease risk. The numerator corresponds to the number of cases geocoded to the census tract, and the denominator of the kernel corresponds to the population of these areas. Using this method, the areas with the highest density of cases were delineated and compared visually with socioeconomic factors, such as average income. RESULTS: The spatial pattern was different in periods of rain compared with periods of drought and did not coincide with the areas considered most at risk for the disease. This study revealed the importance of applying spatial analysis techniques in the field of public health. CONCLUSIONS: These findings indicate that the kernel is a useful tool for obtaining a comprehensive review of the epidemiology of leptospirosis in Aracaju, which supports the kernel's use by the municipal health departments and by the state.

Espacialização da leptospirose em Aracaju, Estado de Sergipe, no período de 2001 a 2007 / Geographical distribution of leptospirosis in Aracaju, State of Sergipe from 2001 to 2007

INTRODUÇÃO: A leptospirose, enfermidade causada por uma espiroqueta patogênica do gênero Leptospira, é uma das zoonoses mais difundidas no mundo, considerada um importante problema de saúde pública. Este trabalho tem como objetivo descrever o padrão espacial da leptospirose na Cidade de Aracaju, no período de 2001 a 2007, buscando identificar as áreas de risco para ocorrência da leptospirose. MÉTODOS: Utilizou-se a razão de Kernel, que consiste na criação de uma razão entre duas superfícies, para visualizar a superfície de risco da doença, onde no numerador coloca-se os casos, georreferenciados para setor censitário, e no denominador o kernel da população dessas áreas. Através deste método, foi possível delimitar áreas de maior densidade de casos, e compará-las visualmente com fator socioeconômico, como renda média. RESULTADOS: Comparando os períodos de chuva com os períodos de seca, verificou-se que não ocorre a presença de padrão espacial semelhante nos dois períodos, não coincidindo com as áreas consideradas de maior risco para ocorrência da doença. Através dos parâmetros estabelecidos, neste estudo, foi permitido verificar a importância da aplicação de técnicas de análise espacial na área de saúde pública. CONCLUSÕES: O kernel se mostrou uma ferramenta útil na obtenção de uma análise global da situação epidemiológica da leptospirose em Aracaju, o que viabiliza sua utilização pelas secretarias de saúde municipal e estadual.

INTRODUCTION: Leptospirosis, a disease caused by pathogenic spirochetes of the genus Leptospira, is one of the most widespread zoonoses in the world and is considered an important public health problem. This paper aims to describe the spatial pattern of leptospirosis in the City of Aracaju from 2001 to 2007 in an effort to identify areas at risk for leptospirosis. METHODS: We used the ratio of Kernel, which represents the ratio between two surfaces, to visualize the surface of disease risk. The numerator corresponds to the number of cases geocoded to the census tract, and the denominator of the kernel corresponds to the population of these areas. Using this method, the areas with the highest density of cases were delineated and compared visually with socioeconomic factors, such as average income. RESULTS: The spatial pattern was different in periods of rain compared with periods of drought and did not coincide with the areas considered most at risk for the disease. This study revealed the importance of applying spatial analysis techniques in the field of public health. CONCLUSIONS: These findings indicate that the kernel is a useful tool for obtaining a comprehensive review of the epidemiology of leptospirosis in Aracaju, which supports the kernel's use by the municipal health departments and by the state.