{"id":217708,"date":"2026-01-06T16:38:10","date_gmt":"2026-01-06T16:38:10","guid":{"rendered":"https:\/\/www.europesays.com\/pt\/217708\/"},"modified":"2026-01-06T16:38:10","modified_gmt":"2026-01-06T16:38:10","slug":"quais-pacientes-apresentam-maior-beneficio-clinico-nos-tratamentos-com-nivolumabe","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/pt\/217708\/","title":{"rendered":"Quais pacientes apresentam maior benef\u00edcio cl\u00ednico nos tratamentos com nivolumabe?"},"content":{"rendered":"<p>A incorpora\u00e7\u00e3o da imunoterapia ao tratamento de primeira linha do c\u00e2ncer gastroesof\u00e1gico avan\u00e7ado representou um avan\u00e7o relevante em um cen\u00e1rio historicamente associado a sobrevida global (SG) inferior a um ano. O estudo\u00a0CheckMate\u00a0649\u00a0(CM-649)\u00a0demonstrou benef\u00edcio significativo de\u00a0SG\u00a0e sobrevida livre de progress\u00e3o com\u00a0<b>nivolumabe\u00a0associado \u00e0 quimioterapia<\/b>\u00a0em pacientes com\u00a0<b>PD-L1 CPS \u2265 5<\/b>, estabelecendo esse regime como padr\u00e3o terap\u00eautico. Em contraste,\u00a0<b>nivolumabe\u00a0+\u00a0ipilimumabe<\/b>\u00a0n\u00e3o atingiu signific\u00e2ncia estat\u00edstica em\u00a0SG. Diante disso,\u00a0em 2025 foi publicada,\u00a0na\u00a0Nature,\u00a0uma an\u00e1lise explorat\u00f3ria\u00a0da popula\u00e7\u00e3o\u00a0CM-649 com o objetivo\u00a0de identificar\u00a0<b>biomarcadores preditivos<\/b>\u00a0capazes de discriminar subgrupos com maior benef\u00edcio cl\u00ednico para cada estrat\u00e9gia imunoter\u00e1pica.\u00a0<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" width=\"1334\" height=\"750\" src=\"https:\/\/www.europesays.com\/pt\/wp-content\/uploads\/2026\/01\/Stock_Firefly_71707_widescreen_1767712492026.jpeg\" class=\"attachment-full size-full wp-post-image\" alt=\"\"  \/><\/p>\n<p><b>Desenho metodol\u00f3gico<\/b>\u00a0<\/p>\n<p>O estudo \u00e9\u00a0<b>an\u00e1lise explorat\u00f3ria p\u00f3s-hoc<\/b>\u00a0baseada\u00a0nas\u00a0an\u00e1lises gen\u00f4micas por\u00a0<b>whole-exome\u00a0sequencing\u00a0(WES)<\/b>\u00a0e\u00a0<b>RNA\u00a0sequencing\u00a0(RNA-seq)<\/b>\u00a0das amostras tumorais da popula\u00e7\u00e3o que recebeu\u00a0quimioterapia +\u00a0nivolumabe,\u00a0nivolumabe\u00a0+\u00a0ipilimumabe\u00a0e quimioterapia isolada, correspondendo a um total de\u00a02394 pacientes analisados.\u00a0As popula\u00e7\u00f5es eram razoavelmente homog\u00eaneas e o tempo de seguimento m\u00ednimo foi de 3 anos.\u00a0Os tumores foram classificados em subtipos moleculares (CIN, GS,\u00a0hipermutado\/MSI-H e EBV-positivo),\u00a0presen\u00e7a de tumor\u00a0mutational\u00a0burden\u00a0(<b>TMB)<\/b>,\u00a0<b>altera\u00e7\u00f5es gen\u00e9ticas\u00a0em\u00a0KRAS<\/b>\u00a0e\u00a0<b>assinaturas de express\u00e3o g\u00eanica\u00a0<\/b>relacionadas a inflama\u00e7\u00e3o, estroma, angiog\u00eanese, hip\u00f3xia, prolifera\u00e7\u00e3o e c\u00e9lulas T reguladoras.\u00a0\u00a0<\/p>\n<p><b>Resultados\u00a0<\/b>\u00a0<\/p>\n<p class=\"content-paywall\">Os resultados demonstraram\u00a0<b>heterogeneidade substancial de benef\u00edcio<\/b>\u00a0conforme o perfil molecular:\u00a0<\/p>\n<ul class=\"content-paywall\">\n<li aria-setsize=\"-1\" data-leveltext=\"\uf0b7\" data-font=\"Symbol\" data-listid=\"2\" data-list-defn-props=\"{&quot;335552541&quot;:1,&quot;335559685&quot;:720,&quot;335559991&quot;:360,&quot;469769226&quot;:&quot;Symbol&quot;,&quot;469769242&quot;:[8226],&quot;469777803&quot;:&quot;left&quot;,&quot;469777804&quot;:&quot;\uf0b7&quot;,&quot;469777815&quot;:&quot;multilevel&quot;}\" data-aria-posinset=\"1\" data-aria-level=\"1\"><b>Tumores\u00a0hipermutados\/MSI-H<\/b>\u00a0apresentaram o maior benef\u00edcio de\u00a0SG\u00a0com terapias baseadas em\u00a0nivolumabe, tanto com quimioterapia quanto com\u00a0ipilimumabe, com\u00a0hazard\u00a0ratios\u00a0consistentemente mais favor\u00e1veis em rela\u00e7\u00e3o \u00e0 quimioterapia isolada.\u00a0<\/li>\n<\/ul>\n<ul class=\"content-paywall\">\n<li aria-setsize=\"-1\" data-leveltext=\"\uf0b7\" data-font=\"Symbol\" data-listid=\"2\" data-list-defn-props=\"{&quot;335552541&quot;:1,&quot;335559685&quot;:720,&quot;335559991&quot;:360,&quot;469769226&quot;:&quot;Symbol&quot;,&quot;469769242&quot;:[8226],&quot;469777803&quot;:&quot;left&quot;,&quot;469777804&quot;:&quot;\uf0b7&quot;,&quot;469777815&quot;:&quot;multilevel&quot;}\" data-aria-posinset=\"2\" data-aria-level=\"1\"><b>EBV-positivo<\/b>\u00a0e\u00a0<b>tumores\u00a0genomicamente\u00a0est\u00e1veis<\/b>\u00a0mostraram tend\u00eancia a maior benef\u00edcio com\u00a0<b>nivolumabe\u00a0+ quimioterapia<\/b>, enquanto tumores\u00a0<b>CIN<\/b>\u00a0derivaram benef\u00edcio mais modesto.\u00a0<\/li>\n<\/ul>\n<ul class=\"content-paywall\">\n<li aria-setsize=\"-1\" data-leveltext=\"\uf0b7\" data-font=\"Symbol\" data-listid=\"2\" data-list-defn-props=\"{&quot;335552541&quot;:1,&quot;335559685&quot;:720,&quot;335559991&quot;:360,&quot;469769226&quot;:&quot;Symbol&quot;,&quot;469769242&quot;:[8226],&quot;469777803&quot;:&quot;left&quot;,&quot;469777804&quot;:&quot;\uf0b7&quot;,&quot;469777815&quot;:&quot;multilevel&quot;}\" data-aria-posinset=\"3\" data-aria-level=\"1\">Altera\u00e7\u00f5es em\u00a0<b>KRAS<\/b>\u00a0estiveram associadas a maior benef\u00edcio de\u00a0SG\u00a0<b>exclusivamente<\/b>\u00a0com\u00a0<b>nivolumabe\u00a0+ quimioterapia<\/b>, n\u00e3o sendo observado o mesmo padr\u00e3o com\u00a0imunoterapia isolada.\u00a0<\/li>\n<\/ul>\n<ul class=\"content-paywall\">\n<li aria-setsize=\"-1\" data-leveltext=\"\uf0b7\" data-font=\"Symbol\" data-listid=\"2\" data-list-defn-props=\"{&quot;335552541&quot;:1,&quot;335559685&quot;:720,&quot;335559991&quot;:360,&quot;469769226&quot;:&quot;Symbol&quot;,&quot;469769242&quot;:[8226],&quot;469777803&quot;:&quot;left&quot;,&quot;469777804&quot;:&quot;\uf0b7&quot;,&quot;469777815&quot;:&quot;multilevel&quot;}\" data-aria-posinset=\"4\" data-aria-level=\"1\">Para\u00a0<b>nivolumabe\u00a0+\u00a0ipilimumabe<\/b>, o benef\u00edcio foi mais evidente em tumores com\u00a0<b>altas assinaturas inflamat\u00f3rias e de c\u00e9lulas T reguladoras (Treg)<\/b>, independentemente do status de PD-L1, sem evid\u00eancia de preju\u00edzo precoce de sobrevida.\u00a0<\/li>\n<\/ul>\n<p class=\"content-paywall\"><strong>Veja tamb\u00e9m:<\/strong> <a href=\"https:\/\/portal.afya.com.br\/oncologia\/checkmate-7fl-associacao-de-nivolumabe-e-quimio-no-cancer-de-mama\" rel=\"nofollow noopener\" target=\"_blank\">CHECKMATE 7FL: associa\u00e7\u00e3o de nivolumabe e quimio no c\u00e2ncer de mama<\/a><\/p>\n<p><b>Para\u00a0refletir<\/b>\u00a0<\/p>\n<p class=\"content-paywall\"><b>\u2013\u00a0Insufici\u00eancia do CPS:<\/b>\u00a0A heterogeneidade\u00a0sugerida\u00a0entre as\u00a0popula\u00e7\u00f5es que derivam mais ou menos benef\u00edcio de imunoterapia, considerando que todas possu\u00edam o biomarcador\u00a0aprovado para a indica\u00e7\u00e3o (CPS\u00a0\u2265 5),\u00a0sugere\u00a0mais uma vez a dificuldade<b>\u00a0<\/b>em se selecionar com robustez os pacientes-alvo dessas medica\u00e7\u00f5es, mesmo\u00a0na oncologia atual,\u00a0molecularmente mais avan\u00e7ada.\u00a0Ainda\u00a0h\u00e1 lacunas de conhecimento significativas\u00a0sobre os\u00a0diferentes mecanismos carcinog\u00eanicos que levam\u00a0\u00e0 doen\u00e7a invasiva, que culminam nas diferentes respostas terap\u00eauticas apresentadas.\u00a0<\/p>\n<p class=\"content-paywall\"><b>\u2013\u00a0O alcance\u00a0da an\u00e1lise\u00a0pos-hoc:<\/b>\u00a0Devemos considerar que uma an\u00e1lise retrospectiva e explorat\u00f3ria\u00a0possui\u00a0limita\u00e7\u00f5es estat\u00edsticas significativas. As sugest\u00f5es levantadas devem ser consideradas encorajadoras para ensaios prospectivos que, de fato,\u00a0levantem maior n\u00edvel de evid\u00eancia.\u00a0<\/p>\n<p><b>O que considerar para a pr\u00e1tica cl\u00ednica<\/b>\u00a0<\/p>\n<p class=\"content-paywall\"><b>Nivolumabe\u00a0+ quimioterapia permanece o padr\u00e3o<\/b>\u00a0em pacientes com CPS \u2265 5.\u00a0Mas,\u00a0os resultados apoiam a hip\u00f3tese de que subgrupos com assinaturas inflamat\u00f3rias espec\u00edficas\u00a0podem se beneficiar\u00a0da individualiza\u00e7\u00e3o\u00a0do regime terap\u00eautico\u00a0com base na\u00a0subtipagem\u00a0molecular, mesmo neste subgrupo.\u00a0\u00c9 prov\u00e1vel\u00a0vermos\u00a0em breve\u00a0an\u00e1lises prospectivas\u00a0de biomarcadores que\u00a0estimulem\u00a0com mais robustez\u00a0esta\u00a0discuss\u00e3o.\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"A incorpora\u00e7\u00e3o da imunoterapia ao tratamento de primeira linha do c\u00e2ncer gastroesof\u00e1gico avan\u00e7ado representou um avan\u00e7o relevante em&hellip;\n","protected":false},"author":2,"featured_media":217709,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[86],"tags":[116,32,33,117],"class_list":{"0":"post-217708","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-saude","8":"tag-health","9":"tag-portugal","10":"tag-pt","11":"tag-saude"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@pt\/115849140864471997","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/pt\/wp-json\/wp\/v2\/posts\/217708","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/pt\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/pt\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/pt\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/pt\/wp-json\/wp\/v2\/comments?post=217708"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/pt\/wp-json\/wp\/v2\/posts\/217708\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/pt\/wp-json\/wp\/v2\/media\/217709"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/pt\/wp-json\/wp\/v2\/media?parent=217708"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/pt\/wp-json\/wp\/v2\/categories?post=217708"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/pt\/wp-json\/wp\/v2\/tags?post=217708"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}