Pembrolizumab
Pembrolizumab
Klass : C
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Produkter
KEYTRUDA, Keytruda, MK-3475
KEYTRUDA, Keytruda, MK-3475ATC-koder
L01FF02
L01FF02Substanser
pembrolizumab
pembrolizumabSammanfattning
Baserat på den kända könsrelaterade dimorfismen i immunsystemet kan patientens kön förväntas att påverka effekten av immunterapier. Omfattningen av fördelarna med pembrolizumab-behandling av avancerat (refraktära eller metastatiska) melanom och skivepitelcellscancer avseende förlängning av överlevnad är könsberoende med bättre resultat för män. Samma trend ses vid avancerad NSCLC och urotelial cancer. Kvinnor är mer benägna att utveckla biverkningar relaterade till immunreaktionsinhibitorer.
Baserat på den kända könsrelaterade dimorfismen i immunsystemet kan patientens kön förväntas att påverka effekten av immunterapier. Omfattningen av fördelarna med pembrolizumab-behandling av avancerat (refraktära eller metastatiska) melanom och skivepitelcellscancer avseende förlängning av överlevnad är könsberoende med bättre resultat för män. Samma trend ses vid avancerad NSCLC och urotelial cancer. Kvinnor är mer benägna att utveckla biverkningar relaterade till immunreaktionsinhibitorer.Background
Generally, women mount stronger innate and adaptive immune responses than men [1]. Since tumors in women have to evade more efficient mechanisms of immune surveillance and undergo a more intensive immuno-editing process to become metastatic [2], advanced tumors in women can be less immunogenic and more resistant to immune therapies [3]. Visa hela bakgrundstexten
Pembrolizumab is an immune checkpoint inhibitor monoclonal antibody that targets the programmed cell death 1 (PD-1) receptor of lymphocytes and blocks its interaction with the ligands PD-L1 and PD-L2 to potentiate an antitumor T-cell response. Pembrolizumab as monotherapy is indicated for the treatment of malign melanoma, metastasized non-small cell lung cancer (NSCLC), refractory primary Hodgkin’s lymphoma, local advanced or metastasized urothelial cancer, and relapsing or metastasized head and neck squamous cell cancer. It’s used either as monotherapy or in combination with platinum-based chemotherapy and pemetrexed is indicated as the first line treatment of metastatic NSCLC of non-squamous type.
Pharmacokinetics and dosing
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Läkemedel innehållande pembrolizumab (ATC-kod L01XC18) används huvudsakligen på sjukhus och därför saknas könsspecifika användningsdata [13].
Referenser
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Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626-38.
Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011;331(6024):1565-70.
Conforti F, Pala L, Bagnardi V, De Pas T, Martinetti M, Viale G et al. Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysis. Lancet Oncol. 2018;19(6):737-746.
KEYTRADA (pembrolizumab). Summary of Product Characteristics. European Medicines Agency (EMA). [updated 2019-02-08, cited 2019-02-18]
Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372(26):2521-32.
Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156-167.
Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016;375(19):1823-1833.
Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A et al. Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. J Clin Oncol. 2019;1(1):JCO1800149.
Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017;376(11):1015-1026.
Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540-50.
McQuade JL, Daniel CR, Hess KR, Mak C, Wang DY, Rai RR et al. Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis. Lancet Oncol. 2018;19(3):310-322.
Menzies AM, Johnson DB, Ramanujam S, Atkinson VG, Wong ANM, Park JJ et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol. 2017;28(2):368-376.
Concise. Kalmar: eHälsomyndigheten. 2015 [cited 2018-12-17.]
- Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626-38.
- Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011;331(6024):1565-70.
- Conforti F, Pala L, Bagnardi V, De Pas T, Martinetti M, Viale G et al. Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysis. Lancet Oncol. 2018;19(6):737-746.
- KEYTRADA (pembrolizumab). Summary of Product Characteristics. European Medicines Agency (EMA). [updated 2019-02-08, cited 2019-02-18]
- Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372(26):2521-32.
- Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156-167.
- Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016;375(19):1823-1833.
- Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A et al. Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. J Clin Oncol. 2019;1(1):JCO1800149.
- Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017;376(11):1015-1026.
- Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540-50.
- McQuade JL, Daniel CR, Hess KR, Mak C, Wang DY, Rai RR et al. Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis. Lancet Oncol. 2018;19(3):310-322.
- Menzies AM, Johnson DB, Ramanujam S, Atkinson VG, Wong ANM, Park JJ et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol. 2017;28(2):368-376.
- Concise. Kalmar: eHälsomyndigheten. 2015 [cited 2018-12-17.]
Uppdaterat
Litteratursökningsdatum: 2/18/2019
Litteratursökningsdatum: 2/18/2019