A combinação de regorafenibe, nivolumabe e quimioterapia é considerada segura e eficaz para vários tipos de câncer, indo para o ensaio de fase 3
Pesquisadores do Memorial Sloan Kettering Cancer Center, em Nova York, concluíram seu ensaio de fase 2 de quimioterapia em combinação com os medicamentos nivolumabe e regorafenibe.
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)
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Pesquisadores do Memorial Sloan Kettering Cancer Center, em Nova York, concluíram seu ensaio de fase 2 de quimioterapia em combinação com os medicamentos nivolumabe e regorafenibe.
As descobertas, “Regorafenibe de primeira linha com nivolumabe e quimioterapia em câncer avançado de esôfago, gástrico ou junção gastroesofágica nos EUA: um estudo de fase 2 de braço único, centro único”, publicado no The Lancet Oncology , sugerem que regorafenibe e nivolumabe com quimioterapia são seguros e demonstram alguma atividade antitumoral em pacientes com câncer esofagogástrico avançado. Com base nesses resultados, está planejado um ensaio clínico randomizado de fase 3 da combinação.
Em estudos anteriores, cada um dos medicamentos demonstrou eficácia potencial contra o adenocarcinoma esofagogástrico. O regorafenibe mostrou-se promissor na melhoria dos resultados no câncer esofagogástrico refratário, o nivolumabe (um anticorpo anti-PD-1) mostrou benefício em combinação com a quimioterapia, e a própria quimioterapia é uma opção de tratamento padrão. Esperava-se que a combinação desses agentes aumentasse a eficácia geral do tratamento, proporcionando potencialmente melhores resultados.
Apesar dos benefícios iniciais da imunoterapia (como o nivolumabe) e da quimioterapia no tratamento do câncer esofagogástrico, muitos pacientes eventualmente desenvolvem resistência terapêutica. A adição de regorafenibe, que pode modular o microambiente tumoral e melhorar as respostas imunológicas, foi uma abordagem estratégica para potencialmente superar ou retardar o desenvolvimento de resistência.
Nivolumabe é um inibidor do ponto de controle imunológico que pode ativar o sistema imunológico do próprio paciente para atingir as células cancerígenas. O regorafenibe, além de seus efeitos antitumorais diretos, pode melhorar a função das células natural killer e das células T CD8 + , ao mesmo tempo que inibe os fatores imunossupressores produzidos pelo tumor.
O câncer esofagogástrico é a segunda principal causa de mortes relacionadas ao câncer, resultando em aproximadamente 1,3 milhão de mortes anualmente. Muitos pacientes são diagnosticados com uma forma metastática da doença, que é difícil de tratar com eficácia, pois se espalha para várias regiões do corpo.
O estudo foi conduzido no Memorial Sloan Kettering Cancer Center com uma amostra final de 35 pacientes. Os participantes receberam um regime de tratamento combinado, incluindo quimioterapia FOLFOX, nivolumabe e regorafenibe oral. O objetivo primário foi a sobrevida livre de progressão em 6 meses e a segurança foi avaliada em todos os pacientes que receberam pelo menos uma dose de qualquer tratamento do estudo.
Na avaliação de 6 meses, 25 dos 35 pacientes avaliáveis (71%) estavam livres de progressão, atingindo o objetivo primário, uma melhoria de 18% em relação ao controle historicamente derivado de 53%.
Avaliações de acompanhamento realizadas aproximadamente 18 meses depois revelaram que o evento adverso mais comum foi a fadiga (92% dos pacientes). Eventos adversos graves ocorreram em 26% dos pacientes, que foram lesão renal aguda (8%), hepatotoxicidade (5%), sepse (5%), pele seca, prurido ou erupção cutânea (3%), náusea (3%), e perfuração gástrica (3%). Não houve mortes relacionadas ao tratamento.
Mais informações: Samuel L Cytryn et al, Regorafenibe de primeira linha com nivolumabe e quimioterapia em câncer avançado de junção esofágica, gástrica ou gastroesofágica nos EUA: um estudo de fase 2 de braço único, centro único, The Lancet Oncology ( 2023). DOI: 10.1016/S1470-2045(23)00358-3
Kazuhiro Shiraishi et al, Imunoterapia combinada em quimioterapia no câncer gástrico, The Lancet Oncology (2023). DOI: 10.1016/S1470-2045(23)00404-7
Informações do periódico: Lancet Oncology