RESUMEN
BACKGROUND: First-line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab-containing regimens in many countries. We report longer-term follow-up data. METHODS: This open-label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression-free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD-L1) expression of ≥1% and then in the overall population. RESULTS: A total of 970 patients were randomly assigned. After 29 months of minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46-0.76]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65-0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48-0.80]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65-0.92]). In patients with tumor cell PD-L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51-0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79-1.36]). Among all treated patients (n = 936), Grade 3-4 treatment-related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. CONCLUSIONS: Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow-up, further supporting use as first-line standard treatment options for patients with advanced ESCC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Ipilimumab , Nivolumab , Humanos , Ipilimumab/administración & dosificación , Ipilimumab/uso terapéutico , Ipilimumab/efectos adversos , Nivolumab/administración & dosificación , Nivolumab/uso terapéutico , Masculino , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Persona de Mediana Edad , Anciano , Estudios de Seguimiento , Adulto , Supervivencia sin Progresión , Antígeno B7-H1/metabolismo , Anciano de 80 o más AñosRESUMEN
OBJECTIVES: To evaluate the efficacy and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma (HCC). METHODS: We analyzed data from a cohort of patients with advanced HCC treated using systemic treatment according to the local institutional protocol. Patients were divided into two groups, Group A, individuals <70 years of age, and Group B, individuals 70 years of age or older at the time of treatment initiation. Efficacy, measured based on overall survival (OS) and time to treatment failure (TTF), and toxicity were compared between groups. RESULTS: A total of 238 patients with advanced HCC who received sorafenib between 2007 and 2018 were evaluated. The median age for Group A was 59.1 years and that for Group B 73.6 years. The major prognostic characteristics were balanced between the groups. There were no significant differences in OS between Group A (8.0 months, 95%CI 6.34-9.3) and Group B (9.0 months, 95%CI 5.38-12.62), p=0.433, or in TTF between Group A (3.0 months, 95%CI 2.39-3.60) and Group B (3.0 months, 95%CI 1.68-4.32), p=0.936. There were no significant differences between Groups A and B with respect to the incidence of adverse events or treatment discontinuation because of toxicity. CONCLUSION: Efficacy and safety of sorafenib did not differ significantly between younger and older patients with HCC. Our data suggest that age alone should not restrict clinical decision-making for patients with advanced HCC.
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Humanos , Persona de Mediana Edad , Anciano , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Antineoplásicos/efectos adversos , Compuestos de Fenilurea/efectos adversos , Pronóstico , Niacinamida/efectos adversos , Sorafenib/efectos adversosRESUMEN
ABSTRACT Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.
RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2015 suas primeiras recomendações sobre a abordagem do CHC. Desde então, novas evidências sobre o diagnóstico e tratamento do CHC foram relatadas na literatura médica, levando a diretoria da SBH a promover uma reunião monotemática sobre câncer primário de fígado em agosto de 2018 com o intuito de atualizar as recomendações sobre o manejo da neoplasia. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização baseada em evidências científicas visando que pudesse nortear a prática clínica multidisciplinar do CHC. O texto resultante foi submetido a avaliação e aprovação de todos membros da SBH através de sua homepage. O documento atual é a versão final que contêm as recomendações atualizadas e revisadas da SBH.
Asunto(s)
Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Sociedades Médicas , Brasil/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/epidemiología , Medicina Basada en la Evidencia , Revisiones Sistemáticas como Asunto , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/epidemiología , Siembra NeoplásicaRESUMEN
OBJECTIVES: With the development of next-generation sequencing (NGS) technologies, DNA sequencing has been increasingly utilized in clinical practice. Our goal was to investigate the impact of genomic evaluation on treatment decisions for heavily pretreated patients with metastatic cancer. METHODS: We analyzed metastatic cancer patients from a single institution whose cancers had progressed after all available standard-of-care therapies and whose tumors underwent next-generation sequencing analysis. We determined the percentage of patients who received any therapy directed by the test, and its efficacy. RESULTS: From July 2013 to December 2015, 185 consecutive patients were tested using a commercially available next-generation sequencing-based test, and 157 patients were eligible. Sixty-six patients (42.0%) were female, and 91 (58.0%) were male. The mean age at diagnosis was 52.2 years, and the mean number of pre-test lines of systemic treatment was 2.7. One hundred and seventy-seven patients (95.6%) had at least one identified gene alteration. Twenty-four patients (15.2%) underwent systemic treatment directed by the test result. Of these, one patient had a complete response, four (16.7%) had partial responses, two (8.3%) had stable disease, and 17 (70.8%) had disease progression as the best result. The median progression-free survival time with matched therapy was 1.6 months, and the median overall survival was 10 months. CONCLUSION: We identified a high prevalence of gene alterations using an next-generation sequencing test. Although some benefit was associated with the matched therapy, most of the patients had disease progression as the best response, indicating the limited biological potential and unclear clinical relevance of this practice.
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Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Genómica/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Análisis de Secuencia de ADN/métodos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Genómica/tendencias , Estimación de Kaplan-Meier , Terapia Molecular Dirigida/métodos , Metástasis de la Neoplasia , Neoplasias/mortalidad , Neoplasias/patología , Medicina de Precisión/métodos , Receptor ErbB-2/antagonistas & inhibidores , Reproducibilidad de los Resultados , Análisis de Secuencia de ADN/tendencias , Factores de Tiempo , Resultado del TratamientoRESUMEN
Objetivo: Este estudo tem por objetivo a validação da escala de Experiência Sexual do Arizona (ASEX), na versão brasileira, como instrumento capaz de identificar disfunção sexual em mulheres portadoras de neoplasia. Métodos: Foram entrevistadas 64 pacientes do sexo feminino com idade média de 47,5 +- 9,8 anos, sendo a maioria da raça branca (64,1 por cento) e casada (73 por cento). Resultados: A comparação da média do total dos valores da escala ASEX entre as pacientes que declararam ser portadoras de disfunção sexual e aquelas que o negaram resultou numa pontuação de 22,84 +- 3,9 vs. 15,1 +- 2,3 respectivamente. Os resultados obtidos em nosso estudo foram semelhantes aos do estudo original de validação da escala. A sensibilidade e a especificidade da ASEX para a identificação de disfunção sexual (escore >= 19) foram de 92 por cento e 98,4 por cento, respectivamente. A área sob a curva (AUC) foi de 0,96. O valor preditivo positivo (VPP) foi 92 por cento e o valor preditivo negativo (VPN), 94,8 por cento. Conclusão: Esses dados demonstram que, apesar das diferenças metodológicas entre os dois estudos, a versão brasileira da ASEX foi capaz de discriminar as pacientes que apresentam disfunção sexual das que não apresentam de maneira similar ao original em inglês.
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Humanos , Femenino , Adulto , Neoplasias de la Mama , Disfunciones Sexuales Psicológicas/diagnóstico , Disfunciones Sexuales Psicológicas/psicología , Psicometría , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Conducta SexualRESUMEN
A consciência de que a prática deve estar fundamentada na postura ética dos profissionais leva à crescente importância de um ensino continuado e aprofundado, que ressalte os valores morais e humanos e o comprometimento social dos estudantes. Buscando adequar-se a esse novo paradigma, estudantes de Medicina da Universidade Federal da Bahia aceitaram a sugestão de criação, em novembro de 2000, de um grupo denominado Academética - Associação de Acadêmicos para o estudo da Ética Médica e Bioética. Os objetivos traçados pela equipe são: continuar o contato com o conteúdo da disciplina Ética Médica, aprofundando e atualizando as discussões acerca de Ética Médica e Bioética, e desenvolver trabalhos ligados a este assunto. As discussões de temas são realizadas através do estudo de artigos, vídeos e estímulo à participação dos estudantes em congressos, palestras e afins. Desta forma, a Academética se constitui em mais uma ferramenta para que os alunos durante a graduação na faculdade de Medicina possam desenvolver o senso crítico e conhecimento acerca de assuntos que englobem a Ética Médica e Bioética.