Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI). RESULTS: The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade ≥ 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003). CONCLUSION: The combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher in those subgroups of patients receiving bolus 5-FU or capecitabine-based chemotherapy plus bevacizumab, when compared to patients treated with infusional %-FU plus bevacizumab (no difference in PFS and OS). Regarding the type of cytotoxic scheme, regimens containing irinotecan and fluoropyrimidine monotherapy showed superior efficacy results when combined to bevacizumab.

Lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in the treatment of HER-2-overexpressing locally advanced or metastatic breast cancer: systematic review and meta-analysis.

BACKGROUND: This paper reports a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy of lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in human epidermal growth factor receptor 2-overexpressing (HER-2+) locally advanced or metastatic breast cancer. METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were progression-free survival and overall survival. The side effects of each treatment were analyzed. The data extracted from the studies were combined by using the hazard ratio or risk ratio with their corresponding 95% confidence interval (CI). RESULTS: A total of 113 references were identified and screened. The final analysis included four trials comprising 1,073 patients with HER-2+. The overall response rate was higher in patients who received the combination of CET plus lapatinib (risk ratio 0.78; 95% CI 0.71-0.85; P < 0.00001) but with significant heterogeneity (χ(2) = 15.61, df = 3; P = 0.001; I(2) = 81%). This result remained favorable to the use of lapatinib when a random-effects model analysis was performed (risk ratio 0.76; 95% CI 0.62-0.94; P = 0.01). Progression-free survival was also higher in patients who received CET plus lapatinib (hazard ratio 0.57; 95% CI 0.49-0.66; P < 0.00001) with no heterogeneity detected on this analysis (χ(2) = 3.05; df = 3; P = 0.38; I(2) = 1%). Overall survival was significantly longer in patients who received CET plus lapatinib (hazard ratio 0.80; 95% CI 0.69-0.92; P = 0.002) without heterogeneity on this analysis (χ(2) = 1.26; df = 3; P = 0.74; I(2) = 0%). Regarding adverse events and severe toxicities (grade ≥3), the group receiving CET plus lapatinib had higher rates of neutropenia (risk ratio 2.08; 95% CI 1.64-2.62; P < 0.00001), diarrhea (risk ratio 4.82; 95% CI 3.14-7.41; P < 0.00001), and rash (risk ratio 8.03; 95% CI 2.46-26.23; P = 0.0006). CONCLUSION: The combination of CET plus lapatinib increased the overall response rate, progression-free survival, and overall survival in patients with HER-2+ locally advanced or metastatic breast cancer.

Implante transcateter de bioprótese valvular pulmonar: revisão sistemática da literatura / Transcatheter pulmonary valve implantation: systematic literature review

A correção cirúrgica de algumas cardiopatias congênitas complexas envolve a reconstrução da via de saída do ventrículo direito com a interposição de homoenxertos, biopróteses, enxertos de jugular bovina ou outros condutos valvulados entre o ventrículo direito e o tronco da artéria pulmonar. Apesar de essas cirurgias poderem ser realizadas com baixa mortalidade, a vida útil das válvulas ou dos condutos implantados é normalmente pequena (< 10 anos), seja por degeneração e/ou calcificação. Graus variáveis de estenose pulmonar na maioria das vezes associada a insuficiência pulmonar são consequências da degeneração dos condutos. Em 2000, Bonhoeffer et al. foram os primeiros a relatar o implante transcateter de bioprótese valvular pulmonar (ITVP) com um dispositivo que posteriormente foi denominado de válvula Melody® (Medtronic, Minneapolis, Estados Unidos). A técnica foi inicialmente desenvolvida para limitar a necessidade de múltiplos procedimentos cirúrgicos, substituindo, em última análise, uma nova troca cirúrgica valvular. Estudos subsequentes na Europa e Estados Unidos atestaram para a segurança e eficácia dessa técnica em um número maior de pacientes. Como a Agência Nacional de Vigilância Sanitária (Anvisa) concedeu a aprovação para o uso clínico da válvula biológica pulmonar transcateter Melody® em fevereiro de 2013, consideramos necessária e oportuna a avaliação judiciosa da utilização dessa nova tecnologia antes que ela fosse aplicada em larga escala em nosso país. O objetivo deste estudo foi realizar uma revisão sistemática da literatura sobre o ITVP em pacientes com disfunções de homoenxertos, condutos valvulados e biopróteses implantados cirurgicamente na via de saída do ventrículo direito.

Surgical repair of some complex congenital heart diseases involves reconstruction of the right ventricular outflow tract using homografts, bioprostheses, bovine jugular grafts or other valved conduits between the right ventricle and the main pulmonary artery. Although these surgical procedures may be performed with low mortality rates, the life span of these implanted valves or conduits is usually short (< 10 years) due to either degeneration and/or calcification. Variable degrees of pulmonary stenosis, often associated with pulmonary insufficiency, are consequences of conduit degeneration. In 2000, Bonhoeffer et al. were the first to report the transcatheter pulmonary valve implantation (TPVI) of a bioprosthetic pulmonary valve later named Melody® valve (Medtronic, Minneapolis, USA). The technique was initially developed to limit the need for multiple surgical procedures, and, ultimately, to work as a surrogate of a new surgical valve replacement. Subsequent clinical studies in Europe and the United States confirmed the safety and efficacy of this technique in a larger number of patients. Since the National Sanitary Surveillance Agency (Agência Nacional de Vigilância Sanitária - Anvisa) granted approval for clinical use of the Melody® transcatheter pulmonary biological valve in February 2103, we deemed that a judicious assessment of this new technology was timely and necessary before the widespread use in our country. The objective of this study was to perform a systematic literature review on the use of TPVI in patients with dysfunctional homografts, valved conduits and bioprostheses implanted surgically in the right ventricular outflow tract.

Implante por cateter de bioprótese valvular aórtica para tratamento de estenose valvar aórtica grave em pacientes inoperáveis sob perspectiva da saúde suplementar: análise de custo-efetividade / Transcatheter aortic valve implantation for the treatment of severe aortic valve stenosis in inoperable patients under the perspective of the brazilian supplemental health system: cost-effectiveness analysis

INTRODUÇÃO: O implante por cateter de bioprótese valvular aórtica (TAVI, do inglês transcatheter aortic valve implantation) constitui nova modalidade de tratamento destinada, sobretudo, aos pacientes com elevado risco cirúrgico. Para esses pacientes, o TAVI resultou em aumento da sobrevivência e melhora da qualidade de vida, comparativamente ao tratamento padrão (medicamentoso, com ou sem valvuloplastia aórtica percutânea). Nosso objetivo foi realizar análise de custo-efetividade da implementação do TAVI no Sistema de Saúde Suplementar brasileiro. MÉTODOS: Foram desenvolvidos um modelo preditivo, para avaliar custo-efetividade real do procedimento em longo prazo, e uma regressão de Weibull com tempo horizonte de 5 e 10 anos, para estimar dados de sobrevida por mais de 24 meses. Adicionalmente, foi desenvolvido modelo de Markov sequencial e determinístico. Resultados foram expressos como razão de custo-efetividade incremental (RCEI) por anos de vida ganhos e anos de vida livres de progressão. RESULTADOS: Para o cenário padrão, no qual o custo da TAVI foi estipulado em R$ 65 mil, o valor da RCEI (custo/ano de vida salvo) em 5 anos foi de R$ 72.520,65. Alterando-se o tempo horizonte para 10 anos, esse valor diminuiu para R$ 41.653,01. CONCLUSÕES: O modelo apontou que o TAVI apresenta efetividade superior e maior custo incremental. Além disso, a incorporação do TAVI no Rol de Procedimentos e Eventos em Saúde da Agência Nacional de Saúde Suplementar acarretaria impacto orçamentário incremental nos próximos 5 anos, variando de R$ 70 milhões a R$ 121 milhões, compatível com o de outras tecnologias já incorporadas no âmbito da Saúde Suplementar.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a new modality of treatment especially dedicated to patients with high surgical risk. In these patients, TAVI increased survival and improved quality of life when compared to standard treatment (drug therapy with or without percutaneous aortic balloon valvuloplasty). Our objective was to perform a cost-efficacy analysis of the implementation of TAVI in the Brazilian Supplemental Health System. METHODS: We developed a predictive model to assess the cost-effectiveness of the procedure in the long-term, and a Weibull regression analysis with a time horizon of 5 and 10 years, to estimate survival data for over 24 months. In addition, a deterministic sequential Markov model was developed. Results were expressed as incremental cost-effectiveness ratio (ICER) per years of life saved and progression-free years of life. RESULTS: In a standard scenario, where the cost of TAVI was estimated as R$ 65 millions, the ICER value (cost/year of life saved) in 5 years was R$ 72,520.65. When the time horizon was adjusted for 10 years, this amount decreased to R$ 41,653.01. CONCLUSIONS: The model indicated that TAVI has superior effectiveness and higher incremental cost. Furthermore, the incorporation of TAVI in the List of Health Procedures and Events of the Brazilian Supplemental Health System would have an incremental budgetary impact over the next 5 years, ranging from R$ 70 millions to R$ 121 millions, consistent with other technologies which have already been incorporated by the system.

Efficacy of palonosetron (PAL) compared to other serotonin inhibitors (5-HT3R) in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately or highly emetogenic (MoHE) treatment: systematic review and meta-analysis.

OBJECTIVE: The objective of this work is to perform a systematic review and meta-analysis of all randomized controlled trials comparing a single intravenous dose of palonosetron (PAL) 0.25 mg with other 5-HT(3)R in patients receiving moderately or highly emetogenic (MoHE) chemotherapy. METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were the incidence of acute and delayed nausea and vomiting. The side effects of each treatment were analyzed. A subgroup analysis was performed to evaluate the influence of the use of corticosteroids. The results are expressed as risk ratio (RR) and the correspondent 95% confidence interval (CI). RESULTS: Five studies were included, with 2057 patients. PAL was compared with ondansetron, granisetron, and dolasetron. Patients in PAL group had less nausea, both acute (RR = 0.86; CI 95% = 0.76 to 0.96; p = 0.007) and delayed (RR = 0.82; CI95% = 0.75 to 0.89; p < 0.00001). They also had less acute vomiting (RR = 0.76; CI 95% = 0.66 to 0.88; p = 0.0002) and delayed vomiting (RR = 0.76; CI95% = 0.68 to 0.85; p < 0.00001). There were no statistical differences in side effects like headache (RR = 0.84; CI 95% = 0.61 to 1.17; p = 0.30), dizziness (RR = 0.40; CI 95% = 0.13 to 1.27; p = 0.12), constipation (RR = 1.29; CI 95% = 0.77 to 2.17; p = 0.33) or diarrhea (RR = 0.67; CI 95% = 0.24 to 1.85; p = 0.44). Patients receiving PAL presented less nausea and vomiting regardless of the use of corticoids. We found no statistical heterogeneity in the global analysis. CONCLUSION: PAL was more effective than the other 5-HT(3)R in preventing acute and delayed CINV in patients receiving MoHE treatments, regardless of the use of concomitant corticosteroids.