肿瘤免疫检查点抑制剂不良反应的监测与处理策略研究进展
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摘要
目前,免疫检查点抑制剂(ICPIs)是继放化疗后恶性肿瘤治疗的重要选择之一,其在多种实体瘤的治疗中都取得了良好的治疗效果。然而,这些药物也可产生广泛的免疫相关性不良反应(irAEs),影响患者的生活质量及预后。因此,护士作为接受免疫治疗患者的主要接触点,需要充分认识irAEs及其适当的处理策略,以改善ICPIs治疗患者的预后及生活质量。本文对肿瘤免疫检查点抑制剂治疗的不良反应及其监测与处理策略进展进行综述。
At present, immunological checkpoint inhibtors(ICPIs) is one of the important choices for the treatment of malignant tumors after radiotherapy and chemotherapy. It has achieved good therapeutic effects in the treatment of various solid tumors. However, these drugs can also produce a wide range of immune-related adverse events(ir AEs), affecting patients′ life quality and prognosis. Therefore, nurses as the main point of contact for immunotherapy patients need to fully understand ir AEs and their appropriate treatment strategies to improve the prognosis and quality of life of patients treated with ICPIs. This article reviews the progress of adverse reactions in the treatment of tumor immunological checkpoint inhibitors and its monitoring and treatment strategies.
At present, immunological checkpoint inhibtors(ICPIs) is one of the important choices for the treatment of malignant tumors after radiotherapy and chemotherapy. It has achieved good therapeutic effects in the treatment of various solid tumors. However, these drugs can also produce a wide range of immune-related adverse events(ir AEs), affecting patients′ life quality and prognosis. Therefore, nurses as the main point of contact for immunotherapy patients need to fully understand ir AEs and their appropriate treatment strategies to improve the prognosis and quality of life of patients treated with ICPIs. This article reviews the progress of adverse reactions in the treatment of tumor immunological checkpoint inhibitors and its monitoring and treatment strategies.
引文
[1]D′Angelo SP,Larkin J,Sosman JA,et al.Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma:A Pooled Analysis[J].J Clin Oncol,2017,35(2):226-235.
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[6]Massard C,Gordon MS,Sharma S,et al.Safety and Efficacy of Durvalumab(MEDI4736),an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor,in Patients With Advanced Urothelial Bladder Cancer[J].J Clin Oncol,2016,34(26):3119-3125.
[7]Angell TE,Min L,Wieczorek TJ,et al.Unique Cytologic Features of Thyroiditis Caused by Immune Checkpoint Inhibitor Therapy for Malignant Melanoma[J].Genes Dis,2017,5(1):46-48.
[8]Motzer RJ,Tannir NM,Mcdermott DF,et al.Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma[J].N Engl J Med,2018,378(14):1277-1290.
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[10]Weber JS,K覿hler KC,Hauschild A.Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab[J].J Clin Oncol,2012,30(21):2691-2697.
[11]Boutros C,Tarhini A,Routier E,et al.Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination[J].Nat Rev Clin Oncol,2016,13(8):473-486.
[12]Villadolid J,Amin A.Immune checkpoint inhibitors in clinical practice:update on management of immune-related toxicities[J].Transl Lung Cancer Res,2015,4(5):560-575.
[13]Antonia SJ,Villegas A,Daniel D,et al.Durvalumab after Chemoradiotherapy in StageⅢNon-Small-Cell Lung Cancer[J].N Engl J Med,2017,377(20):1919-1929.
[14]Teulings HE,Limpens J,Jansen SN,et al.Vitiligo-like depigmentation in patients with stageⅢ-Ⅳmelanoma receiving immunotherapy and its association with survival:a systematic review and meta-analysis[J].J Clin Oncol,2015,33(7):773-781.
[15]Belum VR,Benhuri B,Postow MA,et al.Characterization and management of dermatologic adverse events to agents targeting the PD-1 receptor[J].Eur J Cancer,2016,60:12-25.
[16]Davies M,Duffield EA.Safety of checkpoint inhibitors for cancer treatment:strategies for patient monitoring and management of immune-mediated adverse events[J].Immunotargets Ther,2017,6:51-71.
[17]Rittmeyer A,Barlesi F,Waterkamp D,et al.Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer(OAK):a phase 3,openlabel,multicentre randomised controlled trial[J].Lancet,2016,389(10 066):255-265.
[18]Carbone DP,Reck M,Paz-Ares L,et al.First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer[J].N Engl J Med,2017,39(25):2415-2426.
[19]Eggermont AM,Chiarionsileni V,Grob JJ,et al.Adjuvant ipilimumab versus placebo after complete resection of high-risk stageⅢmelanoma(EORTC 18071):a randomised,double-blind,phase 3 trial[J].Lancet Oncol,2015,16(5):522-530.
[20]Haanen J,Carbonnel F,Robert C,et al.Management of toxicities from immunotherapy:ESMO Clinical Practice Guidelines for diagnosis,treatment and follow-up[J].Ann Oncol,2017,28(suppl_4):iv119-iv142.
[21]Ryder M,Callahan M,Postow MA,et al.Endocrine-related adverse events following ipilimumab in patients with advanced melanoma:a comprehensive retrospective review from a single institution[J].Endocr Relat Cancer,2014,21(2):371-381.
[22]Iwama S,De RA,Callahan MK,et al.Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody[J].Sci Transl Med,2014,6(230):230-245.
[23]Weber JS,D′Angelo SP,Minor D,et al.Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment(CheckMate037):a randomised,controlled,open-label,phase 3 trial[J].Lancet Oncol,2015,16(4):375-384.
[24]Barbee MS,Ogunniyi A,Horvat TZ,et al.Current status and future directions of the immune checkpoint inhibitors ipilimumab,pembrolizumab,and nivolumab in oncology[J].Ann Pharmacother,2015,49(8):907.
[25]Weber JS.Practical management of immune-related adverse events from immune checkpoint protein antibodies for the oncologist[J].Am Soc Clin Oncol Educ Book,2012,32:174-177.
[26]Ledezma B,Heng A.Real-world impact of education:treating patients with ipilimumab in a community practice setting[J].Cancer Manag Res,2013,6:5-14.
[27]Weber J,Gibney G,Kudchadkar RR,et al.PhaseⅠ/Ⅱstudy of metastatic melanoma patients treated with nivolumab who had progressed after ipilimumab[J].Cancer Immunol Res,2016,4(4):345.
[28]Sosa A,Cadena EL,Olive CS,et al.Clinical assessment of immune-related adverse events[J].Ther Adv Med Oncol,2018,10:3861-3966.
[2]Raedler LA.Opdivo(Nivolumab):Second PD-1 Inhibitor Receives FDA Approval for Unresectable or Metastatic Melanoma[J].Am Health Drug Benefits,2015,8(Spec Fea ture):180-183.
[3]Khoja L,Butler MO,Kang SP,et al.Pembrolizumab[J].JImmunother Cancer,2015,3(1):36.
[4]Kythreotou A,Siddique A,Mauri FA,et al.PD-L1[J].J Clin Pathol,2017(12):189-194.
[5]Inman BA,Longo TA,Ramalingam S,et al.Atezolizumab:a PD-L1 blocking antibody for bladder cancer[J].Clin Cancer Res,2017,23(8):1886-1890.
[6]Massard C,Gordon MS,Sharma S,et al.Safety and Efficacy of Durvalumab(MEDI4736),an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor,in Patients With Advanced Urothelial Bladder Cancer[J].J Clin Oncol,2016,34(26):3119-3125.
[7]Angell TE,Min L,Wieczorek TJ,et al.Unique Cytologic Features of Thyroiditis Caused by Immune Checkpoint Inhibitor Therapy for Malignant Melanoma[J].Genes Dis,2017,5(1):46-48.
[8]Motzer RJ,Tannir NM,Mcdermott DF,et al.Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma[J].N Engl J Med,2018,378(14):1277-1290.
[9]Weber JS,Postow M,Lao CD,et al.Management of Adverse Events Following Treatment With Anti-Programmed Death-1 Agents[J].Oncologist,2016,21(10):1230-1240.
[10]Weber JS,K覿hler KC,Hauschild A.Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab[J].J Clin Oncol,2012,30(21):2691-2697.
[11]Boutros C,Tarhini A,Routier E,et al.Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination[J].Nat Rev Clin Oncol,2016,13(8):473-486.
[12]Villadolid J,Amin A.Immune checkpoint inhibitors in clinical practice:update on management of immune-related toxicities[J].Transl Lung Cancer Res,2015,4(5):560-575.
[13]Antonia SJ,Villegas A,Daniel D,et al.Durvalumab after Chemoradiotherapy in StageⅢNon-Small-Cell Lung Cancer[J].N Engl J Med,2017,377(20):1919-1929.
[14]Teulings HE,Limpens J,Jansen SN,et al.Vitiligo-like depigmentation in patients with stageⅢ-Ⅳmelanoma receiving immunotherapy and its association with survival:a systematic review and meta-analysis[J].J Clin Oncol,2015,33(7):773-781.
[15]Belum VR,Benhuri B,Postow MA,et al.Characterization and management of dermatologic adverse events to agents targeting the PD-1 receptor[J].Eur J Cancer,2016,60:12-25.
[16]Davies M,Duffield EA.Safety of checkpoint inhibitors for cancer treatment:strategies for patient monitoring and management of immune-mediated adverse events[J].Immunotargets Ther,2017,6:51-71.
[17]Rittmeyer A,Barlesi F,Waterkamp D,et al.Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer(OAK):a phase 3,openlabel,multicentre randomised controlled trial[J].Lancet,2016,389(10 066):255-265.
[18]Carbone DP,Reck M,Paz-Ares L,et al.First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer[J].N Engl J Med,2017,39(25):2415-2426.
[19]Eggermont AM,Chiarionsileni V,Grob JJ,et al.Adjuvant ipilimumab versus placebo after complete resection of high-risk stageⅢmelanoma(EORTC 18071):a randomised,double-blind,phase 3 trial[J].Lancet Oncol,2015,16(5):522-530.
[20]Haanen J,Carbonnel F,Robert C,et al.Management of toxicities from immunotherapy:ESMO Clinical Practice Guidelines for diagnosis,treatment and follow-up[J].Ann Oncol,2017,28(suppl_4):iv119-iv142.
[21]Ryder M,Callahan M,Postow MA,et al.Endocrine-related adverse events following ipilimumab in patients with advanced melanoma:a comprehensive retrospective review from a single institution[J].Endocr Relat Cancer,2014,21(2):371-381.
[22]Iwama S,De RA,Callahan MK,et al.Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody[J].Sci Transl Med,2014,6(230):230-245.
[23]Weber JS,D′Angelo SP,Minor D,et al.Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment(CheckMate037):a randomised,controlled,open-label,phase 3 trial[J].Lancet Oncol,2015,16(4):375-384.
[24]Barbee MS,Ogunniyi A,Horvat TZ,et al.Current status and future directions of the immune checkpoint inhibitors ipilimumab,pembrolizumab,and nivolumab in oncology[J].Ann Pharmacother,2015,49(8):907.
[25]Weber JS.Practical management of immune-related adverse events from immune checkpoint protein antibodies for the oncologist[J].Am Soc Clin Oncol Educ Book,2012,32:174-177.
[26]Ledezma B,Heng A.Real-world impact of education:treating patients with ipilimumab in a community practice setting[J].Cancer Manag Res,2013,6:5-14.
[27]Weber J,Gibney G,Kudchadkar RR,et al.PhaseⅠ/Ⅱstudy of metastatic melanoma patients treated with nivolumab who had progressed after ipilimumab[J].Cancer Immunol Res,2016,4(4):345.
[28]Sosa A,Cadena EL,Olive CS,et al.Clinical assessment of immune-related adverse events[J].Ther Adv Med Oncol,2018,10:3861-3966.