Segurança e eficácia do pembrolizumabe no câncer de mama triplo negativo
##plugins.themes.bootstrap3.article.sidebar##
Publicado
Jun 3, 2025
##plugins.themes.bootstrap3.article.main##
Resumo
Objetivo: Revisar a eficácia e segurança do fármaco pembrolizumabe no câncer de mama triplo negativo. Métodos: Revisão integrativa nas bases de dados PUBMED, BVS e LILACS, utilizando os descritores “pembrolizumab and triple negative breast cancer” e seus termos alternativos, em língua portuguesa, inglesa e espanhola, filtrando ensaios clínicos randomizados publicados nos últimos cinco anos. Resultados: Foram selecionados dezenove artigos que descreveram a segurança e eficácia do pembrolizumabe no CMTN. O fármaco demonstrou melhores parâmetros de resposta objetiva ao tumor (ORR), sobrevida global (OS) e sobrevida livre de progressão (PFS) comparado à quimioterapia isolada. Quanto à segurança, reações adversas de grau 1 e 2 estiveram presentes podendo limitar o uso do fármaco em populações com doenças imunes, porém foram consideradas leves e demonstraram ser controladas com corticosteroides e medicamentos de suporte. Considerações finais: O pembrolizumabe é uma alternativa eficaz e segura no tratamento de CMTN.
##plugins.themes.bootstrap3.article.details##
Como Citar
Chiba PintoA. P., MoraesM., Regina HahnS., AndrighiF. C., & Modena ZembruskiB. (2025). Segurança e eficácia do pembrolizumabe no câncer de mama triplo negativo. Revista Eletrônica Acervo Saúde, 25(6), e20651. https://doi.org/10.25248/reas.e20651.2025
Seção
Revisão Bibliográfica
Copyright © | Todos os direitos reservados.
A revista detém os direitos autorais exclusivos de publicação deste artigo nos termos da lei 9610/98.
Reprodução parcial
É livre o uso de partes do texto, figuras e questionário do artigo, sendo obrigatória a citação dos autores e revista.
Reprodução total
É expressamente proibida, devendo ser autorizada pela revista.
Referências
1. ADAMS S, et al. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: Cohort A of the phase II KEYNOTE-086 study. Annals of Oncology 2019a; 30(3): 397–404.
2. ADAMS S, et al. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: Cohort B of the phase II KEYNOTE-086 study. Annals of Oncology 2019b; 30(3): 405–11.
3. ANVISA. AGÊNCIA NACIONAL DE VIGILÂNCIA SANITÁRIA. Keytruda® (pembrolizumabe): nova indicação [Internet]. [citado 2023 nov 13]; Available from: https ://www.gov.br/anvisa/pt-br/assuntos/medicamentos/novos-medicamentos-e-indicacoes/keytruda-r-pembrolizumabe-nova-indicacao-4.
4. ANDERS CK, et al. Evaluating the efficacy of a priming dose of cyclophosphamide prior to pembrolizumab to treat metastatic triple negative breast cancer. J Immunother Cancer, 2022; 10(2).
5. CHUN B, et al. Changes in T-cell subsets and clonal repertoire during chemoimmunotherapy with pembrolizumab and paclitaxel or capecitabine for metastatic triple-negative breast cancer. J Immunother Cancer, 2022; 10(1).
6. CONITEC. Diretrizes diagnósticas terapêuticas: carcinoma de mama [Internet]. Brasília: Available from: https ://www.gov.br/conitec/pt-br. 2022.
7. CORTES J, et al. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine, 2022; 387(3): 217–26.
8. CORTES J, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. The Lancet, 2020; 396(10265): 1817–28.
9. DERAKHSHAN F e REIS-FILHO JS. Pathogenesis of Triple-Negative Breast Cancer. Annual Review of Pathology: Mechanisms of Disease, 2021; 17: 181–204.
10. EGELSTON CA, et al. Immunogenicity and efficacy of pembrolizumab and doxorubicin in a phase I trial for patients with metastatic triple-negative breast cancer. Cancer Immunology, Immunotherapy, 2023; 72(9): 3013–27.
11. EISENHAUER EA, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer, 2009; 45(2): 228–47.
12. FASCHING PA, et al. Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer – A single-arm phase II trial (NeoImmunoboost, AGO-B-041). Eur J Cancer, 2023; 184: 1–9.
13. HATTORI M, et al. Pembrolizumab plus chemotherapy in Japanese patients with triple-negative breast cancer: Results from KEYNOTE-355. Cancer Med, 2023; 12(9): 10280–93.
14. HO AY, et al. A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer. Cancer, 2020; 126(4): 850–60.
15. HUANG M, et al. Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. European Journal of Cancer, 2022; 177: 45–52.
16. INCA. INSTITUTO NACIONAL DO CÂNCER. Síntese de Resultados e Comentários [Internet]. Available from: https ://www.gov.br/inca/pt-br/assuntos/cancer/numeros/estimativa/sintese-de-resultados-e-comentarios. 2023.
17. MERCK SHARP & DOHME FARMACÊUTICA LTDA. KEYTRUDA ® [Internet]. Available from: https ://saude.msd.com.br/wp-content/uploads/sites/91/2022/12/keytruda_bula_pro.pdf. 2023.
18. MORRIS GJ, et al. Differences in breast carcinoma characteristics in newly diagnosed African-American and caucasian patients: a single-institution compilation compared with the National Cancer Institute’s surveillance, epidemiology, and end results database. Cancer, 2007; 110(4): 876–84.
19. OLADERU OT, et al. Association of Adjuvant Chemotherapy With Overall Survival Among Women With Small, Node-Negative, Triple-Negative Breast Cancer. JAMA Netw Open, 2020; 3(9): 2016247.
20. SCHMID P, et al. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. New England Journal of Medicine, 2022; 386(6): 556–67.
21. SCHMID P, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. New England Journal of Medicine, 2020a; 382(9): 810–21.
22. SCHMID P, et al. Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: results from the phase 1b open-label, multicohort KEYNOTE-173 study. Annals of Oncology, 2020b; 31(5): 569–81.
23. SHAH M, et al. FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple-Negative Breast Cancer. Clinical Cancer Research, 2022; 28(24): 5249–53.
24. TOLANEY SM, et al. Eribulin plus pembrolizumab in patients with metastatic triple-negative breast cancer (ENHANCE 1): A phase Ib/II study. Clinical Cancer Research, 2021; 27(11): 3061–8.
25. TOPALIAN SL, et al. Immune checkpoint blockade: A common denominator approach to cancer therapy. Cancer Cell, 2015; 27(4): 450–61.
26. VASCONCELOS MC DE HV, et al. Evolução e desenvolvimento do tratamento farmacológico relativo ao câncer de mama triplo negativo: revisão integrativa. Research, Society and Development, 2023; 12(3): 6912340413.
27. VINAYAK S, et al. Open-label Clinical Trial of Niraparib Combined with Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer. JAMA Oncol, 2019; 5(8): 1132–40.
28. WEBER JS, et al. Management of Adverse Events Following Treatment With Anti-Programmed Death-1 Agents. Oncologist, 2016; 21(10): 1230–40.
29. WINER E, et al. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-199): a randomised, open-label, phase 3 trial. The Lancet Oncology, 2021; 22(4): 499–511.
30. XU J. Regulation of cancer immune checkpoints [Internet]. In: Advances in Experimental Medicine and Biology. Available from: http ://www.springer.com/series/5584. 2020.
31. YIN L, et al. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Research, 2020; 22(1).
32. YUAN Y, et al. A Phase II Clinical Trial of Pembrolizumab and Enobosarm in Patients with Androgen Receptor-Positive Metastatic Triple-Negative Breast Cancer. Oncologist, 2021; 26(2): 99-217.
2. ADAMS S, et al. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: Cohort B of the phase II KEYNOTE-086 study. Annals of Oncology 2019b; 30(3): 405–11.
3. ANVISA. AGÊNCIA NACIONAL DE VIGILÂNCIA SANITÁRIA. Keytruda® (pembrolizumabe): nova indicação [Internet]. [citado 2023 nov 13]; Available from: https ://www.gov.br/anvisa/pt-br/assuntos/medicamentos/novos-medicamentos-e-indicacoes/keytruda-r-pembrolizumabe-nova-indicacao-4.
4. ANDERS CK, et al. Evaluating the efficacy of a priming dose of cyclophosphamide prior to pembrolizumab to treat metastatic triple negative breast cancer. J Immunother Cancer, 2022; 10(2).
5. CHUN B, et al. Changes in T-cell subsets and clonal repertoire during chemoimmunotherapy with pembrolizumab and paclitaxel or capecitabine for metastatic triple-negative breast cancer. J Immunother Cancer, 2022; 10(1).
6. CONITEC. Diretrizes diagnósticas terapêuticas: carcinoma de mama [Internet]. Brasília: Available from: https ://www.gov.br/conitec/pt-br. 2022.
7. CORTES J, et al. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine, 2022; 387(3): 217–26.
8. CORTES J, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. The Lancet, 2020; 396(10265): 1817–28.
9. DERAKHSHAN F e REIS-FILHO JS. Pathogenesis of Triple-Negative Breast Cancer. Annual Review of Pathology: Mechanisms of Disease, 2021; 17: 181–204.
10. EGELSTON CA, et al. Immunogenicity and efficacy of pembrolizumab and doxorubicin in a phase I trial for patients with metastatic triple-negative breast cancer. Cancer Immunology, Immunotherapy, 2023; 72(9): 3013–27.
11. EISENHAUER EA, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer, 2009; 45(2): 228–47.
12. FASCHING PA, et al. Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer – A single-arm phase II trial (NeoImmunoboost, AGO-B-041). Eur J Cancer, 2023; 184: 1–9.
13. HATTORI M, et al. Pembrolizumab plus chemotherapy in Japanese patients with triple-negative breast cancer: Results from KEYNOTE-355. Cancer Med, 2023; 12(9): 10280–93.
14. HO AY, et al. A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer. Cancer, 2020; 126(4): 850–60.
15. HUANG M, et al. Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. European Journal of Cancer, 2022; 177: 45–52.
16. INCA. INSTITUTO NACIONAL DO CÂNCER. Síntese de Resultados e Comentários [Internet]. Available from: https ://www.gov.br/inca/pt-br/assuntos/cancer/numeros/estimativa/sintese-de-resultados-e-comentarios. 2023.
17. MERCK SHARP & DOHME FARMACÊUTICA LTDA. KEYTRUDA ® [Internet]. Available from: https ://saude.msd.com.br/wp-content/uploads/sites/91/2022/12/keytruda_bula_pro.pdf. 2023.
18. MORRIS GJ, et al. Differences in breast carcinoma characteristics in newly diagnosed African-American and caucasian patients: a single-institution compilation compared with the National Cancer Institute’s surveillance, epidemiology, and end results database. Cancer, 2007; 110(4): 876–84.
19. OLADERU OT, et al. Association of Adjuvant Chemotherapy With Overall Survival Among Women With Small, Node-Negative, Triple-Negative Breast Cancer. JAMA Netw Open, 2020; 3(9): 2016247.
20. SCHMID P, et al. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. New England Journal of Medicine, 2022; 386(6): 556–67.
21. SCHMID P, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. New England Journal of Medicine, 2020a; 382(9): 810–21.
22. SCHMID P, et al. Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: results from the phase 1b open-label, multicohort KEYNOTE-173 study. Annals of Oncology, 2020b; 31(5): 569–81.
23. SHAH M, et al. FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple-Negative Breast Cancer. Clinical Cancer Research, 2022; 28(24): 5249–53.
24. TOLANEY SM, et al. Eribulin plus pembrolizumab in patients with metastatic triple-negative breast cancer (ENHANCE 1): A phase Ib/II study. Clinical Cancer Research, 2021; 27(11): 3061–8.
25. TOPALIAN SL, et al. Immune checkpoint blockade: A common denominator approach to cancer therapy. Cancer Cell, 2015; 27(4): 450–61.
26. VASCONCELOS MC DE HV, et al. Evolução e desenvolvimento do tratamento farmacológico relativo ao câncer de mama triplo negativo: revisão integrativa. Research, Society and Development, 2023; 12(3): 6912340413.
27. VINAYAK S, et al. Open-label Clinical Trial of Niraparib Combined with Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer. JAMA Oncol, 2019; 5(8): 1132–40.
28. WEBER JS, et al. Management of Adverse Events Following Treatment With Anti-Programmed Death-1 Agents. Oncologist, 2016; 21(10): 1230–40.
29. WINER E, et al. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-199): a randomised, open-label, phase 3 trial. The Lancet Oncology, 2021; 22(4): 499–511.
30. XU J. Regulation of cancer immune checkpoints [Internet]. In: Advances in Experimental Medicine and Biology. Available from: http ://www.springer.com/series/5584. 2020.
31. YIN L, et al. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Research, 2020; 22(1).
32. YUAN Y, et al. A Phase II Clinical Trial of Pembrolizumab and Enobosarm in Patients with Androgen Receptor-Positive Metastatic Triple-Negative Breast Cancer. Oncologist, 2021; 26(2): 99-217.