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Endocrine Adverse Events Of Nivolumab In Non-Small Cell Lung Cancer Patients—Literature Review

M. Dudzińska, M. Szczyrek, K. Wojas-Krawczyk, J. Świrska, I. Chmielewska, A. Zwolak
Published 2020 · Medicine

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In recent years, we have observed significant progress in cancer treatment associated with the development of immunotherapy. A programmed cell death 1 molecule (PD-1) on the surface of T lymphocytes may be stimulated via a specific PD-ligand 1 (PD-L1), which inhibits lymphocyte activation and leads to apoptosis. Some malignant cells are characterized by high PD-L1 expression. Nivolumab, an anti-PD-1 antibody, blocks the interaction between PD-1 and its ligands and inhibits the signaling pathway by preventing the tumor-derived PD-L1 from blocking T lymphocytes. In patients with non-small cell lung cancer (NSCLC), it is used either in monotherapy or in combination with other drugs. Immunotherapy is associated with the possibility of immune-related adverse effects (irAE) including endocrinopathies (3–23%). Thyroid disorders are the most common, with severity rarely exceeding grade 2. Hypophysitis, adrenal insufficiency and diabetes are possible complications which require immediate treatment. Individuals with autoimmune diseases diagnosed prior to immunotherapy are at risk of its exacerbation. In the management of patients receiving immunotherapy, evaluation of history of autoimmune diseases, awareness and early diagnosis of irAE are crucial and may affect treatment outcomes.
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Postępowanie w przypadku wystąpienia endokrynologicznych działań niepożądanych przy stosowaniu leku niwolumab
Maria Stelmachowska-Banaś (2017)
EPAR- Medicine Overview
Opdivo (2020)
ESMO Guidelines Committee. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
J.B.A.G. Haanen (2017)
10.1038/nrendo.2016.205
Cancer immunotherapy — immune checkpoint blockade and associated endocrinopathies
D. J. Byun (2017)
10.1126/science.271.5256.1734
Enhancement of Antitumor Immunity by CTLA-4 Blockade
D. Leach (1996)
10.1093/annonc/mdx225
Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
J. Haanen (2017)
10.2217/imt-2017-0020
A case of fulminant Type 1 diabetes following anti-PD1 immunotherapy in a genetically susceptible patient.
M. Araujo (2017)
10.1111/cen.13063
Immune checkpoint inhibitor‐related hypophysitis and endocrine dysfunction: clinical review
M. Joshi (2016)
Clinical Manifestations of Adrenal Insu ffi ciency in Adults
A. Kotwal
10.1200/JCO.2013.53.0105
Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.
S. Topalian (2014)
10.1056/NEJMoa1504627
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer.
J. Brahmer (2015)
10.1007/s11102-015-0671-4
Immunotherapy and hypophysitis: clinical presentation, treatment, and biologic insights
A. Faje (2015)
10.1001/jamadermatol.2015.1916
Pembrolizumab Cutaneous Adverse Events and Their Association With Disease Progression.
M. Sanlorenzo (2015)
10.1136/bmjdrc-2018-000591
Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes
A. Kotwal (2019)
10.1186/s12916-020-01549-2
Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis
Xiaoxiang Zhou (2020)
Immune - related adverse events as a biomarker in non - melanoma patients treated with programmed cell death 1 inhibitors Opdivo : Immune - Mediated Adverse Reactions Management Guide
S. L. Topalian
10.1200/JCO.2017.77.6385
Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline.
J. Brahmer (2018)
10.1200/JCO.2012.41.6750
Management of immune-related adverse events and kinetics of response with ipilimumab.
J. Weber (2012)
10.1210/jc.2010-1980
High rate of persistent hypothyroidism in a large-scale prospective study of postpartum thyroiditis in southern Italy.
A. Stagnaro-Green (2011)
10.1093/annonc/mdw640
Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer
J. C. Osorio (2017)
10.1016/j.beem.2019.101370
New insight in endocrine-related adverse events associated to immune checkpoint blockade.
G. Elia (2019)
10.1007/s40618-017-0772-1
Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution
F. Guaraldi (2017)
10.1684/ejd.2016.2923
A case of fulminant type 1 diabetes mellitus, with a precipitous decrease in pancreatic volume, induced by nivolumab for malignant melanoma: analysis of HLA and CTLA-4 polymorphisms
K. Ishikawa (2017)
10.1159/000501824
Graves’ Disease Induced by Immune Checkpoint Inhibitors: A Case Report and Review of the Literature
A. Brancatella (2019)
10.1186/s40425-017-0300-z
Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group
I. Puzanov (2017)
10.2217/fon.15.222
Risk of endocrine complications in cancer patients treated with immune check point inhibitors: a meta-analysis.
O. Abdel-Rahman (2016)
10.1016/S1470-2045(15)70054-9
Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial.
N. Rizvi (2015)
Endocrine side e ff ects of cancer immunotherapy
P. Cukier (2017)
10.1210/js.2017-00432
Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study
T. Kobayashi (2018)
10.2337/dc14-2349
Precipitation of Autoimmune Diabetes With Anti-PD-1 Immunotherapy
Jing W Hughes (2015)
10.1002/j.1460-2075.1992.tb05481.x
Induced expression of PD‐1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death.
Y. Ishida (1992)
10.1620/tjem.244.33
Painless Thyroiditis and Fulminant Type 1 Diabetes Mellitus in a Patient Treated with an Immune Checkpoint Inhibitor, Nivolumab.
K. Sakurai (2018)
10.1186/s13256-019-2002-2
Isolated adrenocorticotropic hormone deficiency and thyroiditis associated with nivolumab therapy in a patient with advanced lung adenocarcinoma: a case report and review of the literature
N. Ohara (2019)
10.1001/jamaoncol.2017.3064
Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis
R. Barroso-Sousa (2018)
10.21873/INVIVO.11195
Potential Risk Factors for Nivolumab-induced Thyroid Dysfunction.
H. Yamazaki (2017)
10.1007/s00262-015-1689-1
Anti-programmed cell death-1 therapy and insulin-dependent diabetes: a case report
J. Martin-Liberal (2015)
10.1158/1078-0432.CCR-13-0143
CTLA-4 and PD-1/PD-L1 Blockade: New Immunotherapeutic Modalities with Durable Clinical Benefit in Melanoma Patients
P. Ott (2013)
10.1530/ERC-17-0358
Endocrine side effects of cancer immunotherapy.
Priscilla Cukier (2017)
Immune-Mediated Adverse Reactions Management Guide
Opdivo (2020)
10.1158/2326-6066.CIR-15-0193
Phase I/II Study of Metastatic Melanoma Patients Treated with Nivolumab Who Had Progressed after Ipilimumab
J. Weber (2016)
HIGHLIGHTS OF PRESCRIBING INFORMATION
URSO FORTE. URSO (2007)
10.1186/s40425-019-0729-3
Recovery from secondary adrenal insufficiency in a patient with immune checkpoint inhibitor therapy induced hypophysitis
S. Thapi (2019)
10.2169/internalmedicine.1268-18
Nivolumab-induced Hypophysitis, Secondary Adrenal Insufficiency and Destructive Thyroiditis in a Patient with Lung Adenocarcinoma
Yuka Mishima (2019)
10.1200/JCO.2015.66.1389
Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma.
J. Weber (2017)
10.1073/pnas.1908079116
Autoimmune antibodies correlate with immune checkpoint therapy-induced toxicities
Salahaldin A. Tahir (2019)
10.1200/JOP.18.00005
Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline Summary.
J. Brahmer (2018)
10.1371/journal.pone.0216954
Incidence, features, and prognosis of immune-related adverse events involving the thyroid gland induced by nivolumab
I. Yamauchi (2019)
10.1016/j.lpm.2018.10.019
Incidence of thyroid dysfunctions during treatment with nivolumab for non-small cell lung cancer: Retrospective study of 105 patients.
Pauline Campredon (2019)
10.1056/NEJMoa1507643
Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.
H. Borghaei (2015)
10.1038/nrc3239
The blockade of immune checkpoints in cancer immunotherapy
D. Pardoll (2012)
Disease Induced by Immune Checkpoint Inhibitors: A Case Report and Review of the Literature
A Brancatella (2019)
10.1111/1346-8138.13028
Serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab
T. Narita (2016)
10.1200/JCO.2014.60.0379
Toxicities of Immunotherapy for the Practitioner.
J. Weber (2015)
10.1007/s00262-017-2033-8
Autoimmune diabetes induced by PD-1 inhibitor—retrospective analysis and pathogenesis: a case report and literature review
Marie-Léa Gauci (2017)
10.1056/NEJMoa1412082
Nivolumab in previously untreated melanoma without BRAF mutation.
C. Robert (2015)
10.1016/j.jtho.2017.08.022
Early Immune‐Related Adverse Events and Association with Outcome in Advanced Non‐Small Cell Lung Cancer Patients Treated with Nivolumab: A Prospective Cohort Study
Shunsuke Teraoka (2017)
10.1007/s40618-016-0439-3
Late-onset panhypopituitarism in a 72-year-old male patient treated with ipilimumab for metastatic melanoma: a case report
G. Vancieri (2016)
10.1016/j.str.2015.09.010
Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1.
K. Zak (2015)
10.1200/JCO.2016.66.9929
Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer.
S. Gettinger (2016)
10.1016/j.ejca.2016.12.038
Programmed cell death protein-1 (PD-1) inhibitor therapy in patients with advanced melanoma and preexisting autoimmunity or ipilimumab-triggered autoimmunity.
R. Gutzmer (2017)
Programmed cell death protein-1 (PD-1) inhibitor therapy in patients with advanced melanoma and preexisting autoimmunity or ipilimumab-triigered autoimmunity
R. Gutzmer (2017)
10.1016/S0140-6736(15)01281-7
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial
R. Herbst (2016)
10.1093/jjco/hyx018
Isolated ACTH deficiency probably induced by autoimmune-related mechanism evoked with nivolumab
K. Kitajima (2017)
10.1136/bcr-2018-228135
Nivolumab-induced hypophysitis leading to hypopituitarism and secondary empty sella syndrome in a patient with non-small cell lung cancer
J. Chang (2019)
Clinical Features of Nivolumab - Induced
I. Yamauchi
10.1089/thy.2016.0562
Clinical Features of Nivolumab-Induced Thyroiditis: A Case Series Study.
I. Yamauchi (2017)
10.1159/000456540
Autoimmune Diabetes and Thyroiditis Complicating Treatment with Nivolumab
L. Li (2017)
10.1080/2162402X.2016.1231292
Characterization of nivolumab-associated skin reactions in patients with metastatic non-small cell lung cancer
O. Hasan Ali (2016)
10.2169/internalmedicine.8548-16
Isolated Adrenocorticotropic Hormone Deficiency Caused by Nivolumab in a Patient with Metastatic Lung Cancer
Kazuhiko Takaya (2017)
10.14310/horm.2002.1754
Endocrine sequelae of immune checkpoint inhibitors
G. Ntali (2017)
10.1016/j.coi.2011.12.009
Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity.
Suzanne L. Topalian (2012)
10.1530/ERC-13-0499
Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution.
Mabel M Ryder (2014)
10.3390/cancers11111784
Is there an Exposure–Response Relationship for Nivolumab in Real-World NSCLC Patients?
A. Bellesoeur (2019)
10.1158/1078-0432.CCR-15-1136
Nivolumab in Resected and Unresectable Metastatic Melanoma: Characteristics of Immune-Related Adverse Events and Association with Outcomes
Morganna Freeman-Keller (2015)
10.1210/jc.2012-4075
Endocrine side effects induced by immune checkpoint inhibitors.
S. Corsello (2013)
10.1530/EDM-16-0108
Hyponatraemia secondary to nivolumab-induced primary adrenal failure
Harris Trainer (2016)
10.1016/j.endinu.2018.05.005
Nivolumab-induced thyroid dysfunction in patients with lung cancer.
A. Ramos-Leví (2019)
10.1016/j.lungcan.2017.11.019
Correlation between immune-related adverse events and efficacy in non-small cell lung cancer treated with nivolumab.
K. Sato (2018)
Transient thyrotoxicosis during nivolumab treatment.
M. van Kooten (2017)
Diabetes Mellitus in a Patient Treated with an Immune Checkpoint Inhibitor
(2018)
10.1016/j.cellimm.2016.09.009
PD-1/PD-L and autoimmunity: A growing relationship.
M. Zamani (2016)
10.1210/jc.2017-00448
Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms
Danae A Delivanis (2017)
10.1056/NEJMoa1510665
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.
R. Motzer (2015)
10.1111/j.1600-6143.2012.04224.x
Role of the PD‐1 Pathway in the Immune Response
L. Riella (2012)
Common Terminology Criteria for Adverse Events (CTCAE); Version 5; National Cancer Institute: Bethesda
Nivolumab-induce hypophysitis leading to hypopituitarism and secondary empty sella syndrome in a patient with non-small cell lung cancer
J. Chang (2019)
10.1530/EJE-19-0291
Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review
Jeroen M K de Filette (2019)
10.1007/s40618-019-01112-8
Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study
E. M. Presotto (2019)
10.1126/scitranslmed.3008002
Pituitary Expression of CTLA-4 Mediates Hypophysitis Secondary to Administration of CTLA-4 Blocking Antibody
Shintaro Iwama (2014)
10.1634/theoncologist.2017-0133
Immune-Related Adverse Events as a Biomarker in Non-Melanoma Patients Treated with Programmed Cell Death 1 Inhibitors.
J. Judd (2017)
10.1634/theoncologist.2017-0384
Association of Immune-Related Adverse Events with Clinical Benefit in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Nivolumab.
Yukihiro Toi (2018)
10.1634/theoncologist.2016-0189
Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.
Benjamin Herzberg (2017)
10.1210/JC.2016-2300
Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab
Jeroen de Filette (2016)
10.1507/ENDOCRJ.EJ12-0161
Reversible impairment of the processing of proopiomelanocortin into ACTH in pituitary enlargement suspected of lymphocytic hypophysitis.
H. Akahori (2012)
10.1159/000485742
Severe Inflammatory Ophthalmopathy in a Euthyroid Patient during Nivolumab Treatment
Pauline Campredon (2018)
A case series study
Kun Lv (2020)
10.1186/s40425-016-0196-z
Genetic risk analysis of a patient with fulminant autoimmune type 1 diabetes mellitus secondary to combination ipilimumab and nivolumab immunotherapy
J. Lowe (2016)
10.1056/NEJMoa1200690
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
S. Topalian (2012)
10.1056/NEJMc1509660
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
M. Valsecchi (2015)
10.1007/s12020-019-01871-7
Thyroid dysfunction induced by nivolumab: searching for disease patterns and outcomes
I. Peiró (2019)
Immunologia i immunoterapia niedrobnokomórkowego raka płuca
K. Wojas-Krawczyk (2017)
10.15226/2374-6890/3/1/00143
Thyroid-Induced Toxicity of Check-Point Inhibitors Immunotherapy in the Treatment of Advanced Non-Small Cell Lung Cancer
E. Rossi (2016)
10.1136/bcr-2019-231236
Nivolumab-induced hypothyroidism followed by isolated ACTH deficiency
Catarina Martins Machado (2019)
10.1038/nature14011
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
R. Herbst (2014)
10.2217/imt-2016-0147
Risk of endocrine adverse events in cancer patients treated with PD-1 inhibitors: a systematic review and meta-analysis.
Y. Shang (2017)
10.1111/fcp.12423
Thyroiditis and immune check point inhibitors: the post‐marketing experience using the French National Pharmacovigilance database
J. Garon-Czmil (2019)
Immunologia i immunoterapia niedrobnokomórkowego raka płuca. Nowotw. Płuca Klatki Piersiowej
K Wojas-Krawczyk (2017)
Bethesda, MD, USA, 2003
Common Terminology Criteria for Adverse Events (2020)
10.1056/NEJMoa1302369
Nivolumab plus ipilimumab in advanced melanoma.
J. Wolchok (2013)
10.1507/endocrj.EJ19-0076
Nivolumab-induced hypophysitis causing secondary adrenal insufficiency after transient ACTH elevation.
Tomonori Sekizaki (2019)
10.1186/s40425-017-0245-2
Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic lung cancer
J. Godwin (2017)
10.1001/jamaoncol.2017.2925
Association of Immune-Related Adverse Events With Nivolumab Efficacy in Non–Small-Cell Lung Cancer
K. Haratani (2018)
10.2337/dc20-S002
2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020
(2019)
Secondary Adrenal Insufficiency Following Nivolumab Therapy in a Patient with Metastatic Renal Cell Carcinoma.
Toshiro Seki (2017)
10.1136/bmj.2.5416.1024
Nobel Prize
P. Wilhelm (1964)



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