O uso de inibidores de checkpoint imunológico na imunoterapia do câncer gástrico
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Jun 7, 2024
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Resumo
Objetivo: Abordar o uso de inibidores de checkpoint imunológico (ICI) na imunoterapia do câncer gástrico (CG). Revisão bibliográfica: A principal modalidade terapêutica do CG é o tratamento cirúrgico, sendo a única opção curativa. Entretanto, a imunoterapia com o uso de ICI tem sido uma nova estratégia de tratamento para neoplasias malignas. Os principais pontos de verificação imunológicos são: PD-1, PD-L1 e o CTLA-4; o bloqueio seletivo desses pontos de controle inibitórios pode permitir a ativação contínua de células T, promovendo respostas antitumorais eficazes. O estudo KEYNOTE-059 demonstrou que PD-L1 possui atividade antitumoral e foi bem tolerado em monoterapia e em combinação com quimioteraPIA. O estudo KEYNOTE-061 e 062 demonstraram aumento da taxa de sobrevida geral e maior perfil de segurança para os pacientes, com maior duração de resposta. O estudo CHECKMATE-0649 demonstrou que o Nivolumab e quimioterapia tiveram melhor sobrevida geral em relação a quimioterapia isolada (13,1 vs. 11,1 meses) com progressão livre de doença em 12 meses de 36%. Considerações finais: Ensaios clínicos indicaram resultados promissores com essa nova abordagem para o CG, porém, apesar disso, ainda existem limitações, como a irresponsividade em alguns casos e a presença de efeitos colaterais significantes.
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Como Citar
LopesG. V., do Nascimento FilhoF. H. W. de M., & SobrinhoH. M. da R. (2024). O uso de inibidores de checkpoint imunológico na imunoterapia do câncer gástrico. Revista Eletrônica Acervo Saúde, 24(6), e16684. https://doi.org/10.25248/reas.e16684.2024
Seção
Revisão Bibliográfica
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Referências
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13. JANJIGIAN YY, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. The Lancet, 2021; 398(10294): 27-49.
14. KANG YK, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet, 2017; 390(10111): 2461–2471.
15. KANG YK, et al. PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer. Journal of Clinical Oncology, 2021; 39(26): 2903–2913.
16. KANG YK, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology, 2022; 23(2): 234–247.
17. LI X, et al. Research progress in targeted therapy and immunotherapy for gastric cancer. Chinese Medical Journal, 2022; 135(11): 1299–1313.
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19. MACHLOWSKA J, et al. Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies. International Journal of Molecular Sciences, 2020; 21(11): 4012.
20. MARIN-ACEVEDO JA, et al. Next generation of immune checkpoint inhibitors and beyond. Journal of hematology & oncology, 2021; 14(1): 45.
21. MOGHIMI M, et al. Association of IL-8 -251T>A (rs4073) polymorphism with susceptibility to gastric cancer: a systematic review and meta-analysis based on 33 case-control studies. Arquivos de Gastroenterologia, 2020; 57(1): 91–99.
22. PETRYSZYN P, et al. Gastric Cancer: Where Are We Heading? Digestive Disea, 2020; 38(4): 280–285.
23. RUSSO AE e STRONG VE. Gastric Cancer Etiology and Management in Asia and the West. Annual review of medicine, 2019; 70: 353–367.
24. SEENEEVASSEN L, et al. Gastric Cancer: Advances in Carcinogenesis Research and New Therapeutic Strategies. International journal of molecular sciences, 2021; 22(7).
25. SEXTON RE, et al. Gastric cancer: a comprehensive review of current and future treatment strategies. Cancer metastasis reviews, 2020; 39(4): 1179–1203.
26. SHITARA K, et al. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA oncology, 2020; 6(10): 1571–1580.
27. STEIN A, et al. Efficacy of Ipilimumab vs FOLFOX in Combination with Nivolumab and Trastuzumab in Patients with Previously Untreated ERBB2-Positive Esophagogastric Adenocarcinoma: The AIO INTEGA Randomized Clinical Trial. JAMA oncology, 2022; 8(8):1150–1158.
28. SUN S, et al. Identification of AKIRIN2 as a potential biomarker and correlation with immunotherapy in gastric adenocarcinoma by integrated bioinformatics analysis. Scientific reports, 2022; 12(1): 8400.
29. TINTELNOT J, et al. Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic Esophagogastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217). BMC Cancer, 2020; 20(1): 503.
30. TAIEB J, et al. Evolution of checkpoint inhibitors for the treatment of metastatic gastric cancers: Current status and future perspectives. Cancer treatment reviews, 2018; 66:104-113.
31. VRÁNA D, et al. From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer. International Journal of Molecular Sciences, 2018; 20(1): 13.
32. WEI SC, et al. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discovery, 2018; 8(1):1069-1086.
33. XIE J, et al. Immunotherapy of gastric cancer: Past, future perspective and challenges. Pathology
- Research and Practice, 2021; 218: 53322.
34. ZHAO SL e FANG JY. The Role of Postoperative Adjuvant Chemotherapy Following Curative Resection for Gastric Cancer: A Meta-Analysis. Cancer Investigation, 2008; 26(3): 317–325.
35. REIS AP e MACHADO JAN. Imunoterapia no câncer - inibidores do checkpoint imunológico. Arq Asma Alerg Imunol. 2020;4(1):72-77.
2. ABBAS AK, et al. Imunologia Celular e Molecular. 10 ed. Rio de Janeiro: GEN Guanabara Koogan, 2023; 632p.
3. BANG YJ, et al. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2019; 22(4): 828–837.
4. BRASIL. Ministério da Saúde. DATASUS. Tabnet. Brasília, DF: Ministério da Saúde, 2021. Disponível em: https://datasus.saude.gov.br/informacoes-de-saude-tabnet/. Acessado em: 01 de fevereiro de 2024.
5. BRASIL. Ministério da Saúde. Diretrizes Diagnósticas e Terapêuticas Adenocarcinoma de Estômago, 2018. Disponível em: https://www.gov.br/saude/pt-br/assuntos/pcdt/arquivos/2018/portaria_conjunta_n3_adenocarcinoma_de_estomago-15-01-2018.pdf. Acessado em: 01 de fevereiro de 2024.
6. FUCHS CS, et al. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2022; 25 (1):197–206.
7. GULLO I, et al. Precancerous lesions of the stomach, gastric cancer and hereditary gastric cancer syndromes. Pathologica, 2020; 112(3): 166–185.
8. HÖGNER A e MOEHLER M. Immunotherapy in Gastric Cancer. Current oncology, 2022; 29(3):1559–1574.
9. HÖGNER A e THUSS-PATIENCE P. Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma. Pharmaceuticals (Basel), 2021; 14(2): 151.
10. HUO G, et al. Efficacy of PD-1/PD-L1 inhibitors in gastric or gastro-oesophageal junction cancer based on clinical characteristics: a meta-analysis. BMC Cancer, 2023; 23(1):143.
11. JIN X, et al. Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer. Frontiers in Immunology, 2022; 13.
12. JOSHI SS e BADGWELL BD. Current treatment and recent progress in gastric cancer. CA: a cancer journal for clinicians, 2021; 71(3): 264–279.
13. JANJIGIAN YY, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. The Lancet, 2021; 398(10294): 27-49.
14. KANG YK, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet, 2017; 390(10111): 2461–2471.
15. KANG YK, et al. PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer. Journal of Clinical Oncology, 2021; 39(26): 2903–2913.
16. KANG YK, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology, 2022; 23(2): 234–247.
17. LI X, et al. Research progress in targeted therapy and immunotherapy for gastric cancer. Chinese Medical Journal, 2022; 135(11): 1299–1313.
18. LIU L e DENG W. Gastric Cancer: Innovations in Screening, Diagnosis and Treatment. Journal of personalized medicine, 2023; 13(1).
19. MACHLOWSKA J, et al. Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies. International Journal of Molecular Sciences, 2020; 21(11): 4012.
20. MARIN-ACEVEDO JA, et al. Next generation of immune checkpoint inhibitors and beyond. Journal of hematology & oncology, 2021; 14(1): 45.
21. MOGHIMI M, et al. Association of IL-8 -251T>A (rs4073) polymorphism with susceptibility to gastric cancer: a systematic review and meta-analysis based on 33 case-control studies. Arquivos de Gastroenterologia, 2020; 57(1): 91–99.
22. PETRYSZYN P, et al. Gastric Cancer: Where Are We Heading? Digestive Disea, 2020; 38(4): 280–285.
23. RUSSO AE e STRONG VE. Gastric Cancer Etiology and Management in Asia and the West. Annual review of medicine, 2019; 70: 353–367.
24. SEENEEVASSEN L, et al. Gastric Cancer: Advances in Carcinogenesis Research and New Therapeutic Strategies. International journal of molecular sciences, 2021; 22(7).
25. SEXTON RE, et al. Gastric cancer: a comprehensive review of current and future treatment strategies. Cancer metastasis reviews, 2020; 39(4): 1179–1203.
26. SHITARA K, et al. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA oncology, 2020; 6(10): 1571–1580.
27. STEIN A, et al. Efficacy of Ipilimumab vs FOLFOX in Combination with Nivolumab and Trastuzumab in Patients with Previously Untreated ERBB2-Positive Esophagogastric Adenocarcinoma: The AIO INTEGA Randomized Clinical Trial. JAMA oncology, 2022; 8(8):1150–1158.
28. SUN S, et al. Identification of AKIRIN2 as a potential biomarker and correlation with immunotherapy in gastric adenocarcinoma by integrated bioinformatics analysis. Scientific reports, 2022; 12(1): 8400.
29. TINTELNOT J, et al. Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic Esophagogastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217). BMC Cancer, 2020; 20(1): 503.
30. TAIEB J, et al. Evolution of checkpoint inhibitors for the treatment of metastatic gastric cancers: Current status and future perspectives. Cancer treatment reviews, 2018; 66:104-113.
31. VRÁNA D, et al. From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer. International Journal of Molecular Sciences, 2018; 20(1): 13.
32. WEI SC, et al. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discovery, 2018; 8(1):1069-1086.
33. XIE J, et al. Immunotherapy of gastric cancer: Past, future perspective and challenges. Pathology
- Research and Practice, 2021; 218: 53322.
34. ZHAO SL e FANG JY. The Role of Postoperative Adjuvant Chemotherapy Following Curative Resection for Gastric Cancer: A Meta-Analysis. Cancer Investigation, 2008; 26(3): 317–325.
35. REIS AP e MACHADO JAN. Imunoterapia no câncer - inibidores do checkpoint imunológico. Arq Asma Alerg Imunol. 2020;4(1):72-77.