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Terapêutica com Cetuximab em adenocarcinoma gástrico metastático com amplificação EGFR : a propósito de um caso clínico
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O cancro gástrico é um dos cinco tumores mais frequentes a nível mundial, constituindo a quarta principal causa de morte por cancro. A sua morbimortalidade associa-se, frequentemente, ao diagnóstico tardio. No contexto metastático, a pesquisa de biomarcadores tumorais como HER2, PD-L1 e instabilidade de microssatélites, permite dirigir o tratamento e melhorar, significativamente, a sobrevivência dos doentes.
Neste contexto, será apresentado um caso de um indivíduo de 44 anos, diagnosticado com um adenocarcinoma gástrico com metastização do sistema nervoso central, ganglionar e hepática ab initium em setembro de 2021. Perante ausência de expressão de HER2, PD-L1 ou instabilidade de microssatélites, foi solicitado um Painel Next Generation Sequencing, que identificou uma amplificação do recetor do fator de crescimento epitelial (EGFR). Após progressão de doença sob 1ª linha de quimioterapia (Fluoropirimidina/Oxaliplatina), e discussão em Molecular Tumor Board, embora a evidência no momento fosse escassa, em agosto de 2022, iniciou 2ª linha terapêutica com Irinotecano/Cetuximab (anti-EGFR), mantendo este esquema durante 17 meses, até janeiro de 2024, com boa resposta e tolerância. Por nova evidência de progressão de doença, em janeiro de 2024, foi alterado para Paclitaxel/Cetuximab, o qual manteve até à data da última avaliação, no âmbito deste trabalho, em março de 2024, com aparente resposta e tolerância.
Apesar de vários ensaios clínicos de fase III não demonstrarem benefício na associação de terapêutica anti-EGFR à quimioterapia standard utilizada em adenocarcinoma gástrico metastático, estudos mais recentes indicam que estes poderão ter benefício em populações molecularmente selecionadas, isto é, com amplificação de EGFR. A apresentação deste caso permite discutir a abordagem ao adenocarcinoma gástrico metastático com amplificação EGFR e o papel do NGS neste tipo de neoplasia.
Gastric cancer is one of the fifth most common tumors worldwide and is the fourth leading cause of death by cancer. Its morbility and mortality is often associated with late diagnosis. In the metastatic context, the search for tumor biomarkers such as HER2, PD-L1 and microssatelite instability makes it possible to direct treatment and significantly improves patient survival. In this context, we will present the case report of a 44-year-old man diagnosed with gastric adenocarcinoma with central nervous system, lymph node and liver metastasis ab initium in September 2021. In the absence of HER2 expression, PD-L1 expression or microssatellite instability, a next Generation Sequencing panel was requested, which identified an amplification of the epithelial growth factor receptor (EGFR). After disease progression under first line of chemotherapy (fluoropymirimidine/oxaliplatin), and discussion at the Molecular Tumor Board, although the low evidence at the time, in August 2022, the patient started second line therapy with irinotecan/cetuximab (anti-EGFR), maintaining this regimen along 17 months, until January 2024, with good response and tolerance. Due to new evidence of disease progression, in January 2024, he was switched to Paclitaxel/Cetuximab, which he has maintained until the date of the last evalution in this study, in March 2024, with an apparent response and tolerance. Although several phase III clinical trials have shown no benefit in the association of anti-EGFR therapy with standard chemotherapy used in metastatic gastric adenocarcinoma, more recent studies show that it may have a benefit in molecularly selected populations with EGFR amplification. The report of this case allows us to discuss the approach to metastatic gastric adenocarcinoma with EGFR amplification and the role of NGS in this type of cancer.
Gastric cancer is one of the fifth most common tumors worldwide and is the fourth leading cause of death by cancer. Its morbility and mortality is often associated with late diagnosis. In the metastatic context, the search for tumor biomarkers such as HER2, PD-L1 and microssatelite instability makes it possible to direct treatment and significantly improves patient survival. In this context, we will present the case report of a 44-year-old man diagnosed with gastric adenocarcinoma with central nervous system, lymph node and liver metastasis ab initium in September 2021. In the absence of HER2 expression, PD-L1 expression or microssatellite instability, a next Generation Sequencing panel was requested, which identified an amplification of the epithelial growth factor receptor (EGFR). After disease progression under first line of chemotherapy (fluoropymirimidine/oxaliplatin), and discussion at the Molecular Tumor Board, although the low evidence at the time, in August 2022, the patient started second line therapy with irinotecan/cetuximab (anti-EGFR), maintaining this regimen along 17 months, until January 2024, with good response and tolerance. Due to new evidence of disease progression, in January 2024, he was switched to Paclitaxel/Cetuximab, which he has maintained until the date of the last evalution in this study, in March 2024, with an apparent response and tolerance. Although several phase III clinical trials have shown no benefit in the association of anti-EGFR therapy with standard chemotherapy used in metastatic gastric adenocarcinoma, more recent studies show that it may have a benefit in molecularly selected populations with EGFR amplification. The report of this case allows us to discuss the approach to metastatic gastric adenocarcinoma with EGFR amplification and the role of NGS in this type of cancer.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2024
Palavras-chave
Gastric cancer Metastasis Molecular targeted therapy Cetuximab Gene amplification