Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ adverse effects
Antineoplastic Agents, Immunological
/ adverse effects
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Female
Humans
Kidney Neoplasms
/ drug therapy
Lung Neoplasms
/ drug therapy
Male
Melanoma
/ drug therapy
Middle Aged
Nivolumab
/ adverse effects
Retrospective Studies
Skin Neoplasms
/ drug therapy
Thyroid Diseases
/ chemically induced
Young Adult
Cancer
Endocrine toxicity
Immunotherapy
Nivolumab
Pembrolizumab
Journal
Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
12
06
2019
accepted:
03
09
2019
pubmed:
23
9
2019
medline:
21
11
2020
entrez:
23
9
2019
Statut:
ppublish
Résumé
The immune checkpoint inhibitors (ICPIs) agents anti-T lymphocytes-associated antigen 4 (CTLA-4) and anti-programmed cell death protein-1 (PD-1) and its ligands (PD-L1/PD-L2) have opened a new scenario in the treatment of cancer. These agents can induce immuno-related adverse events (irAEs), which may affect the endocrine system. The aim of this study was to analyze the occurrence and the course of endocrine irAEs in cancer patients treated with anti-PD-1 immunotherapy. This was a retrospective, multicentre study, involving cancer patients treated with the PD-1 inhibitors nivolumab or pembrolizumab at reference Oncology Centres. One hundred and seventy-nine consecutive patients with different types of cancer (mostly non-small cell lung cancer, melanoma, kidney cancer) were included in the study. Patients had received nivolumab (70.9%) or pembrolizumab (29.1%) for 2-33 months. The study evaluated clinical data records until the established date of July 15, 2018. The primary end point was the assessment of endocrine toxicity and possible predictive factors. Endocrine toxicity occurred in 54 out of 179 patients (30.2%) and was related to thyroid dysfunction, with the exception of one case of diabetes mellitus. Thyroid toxicity occurred mostly within 2 months from the initiation of immunotherapy (83% of cases). A pre-existing thyroid dysfunction was a significant predictor of disease flare. Thyroid alterations are frequently associated with anti PD-1 treatment in cancer patients. Regular thyroid assessment should be performed, particularly in the first months of treatment and in patients with a pre-existing thyroid disease.
Identifiants
pubmed: 31542865
doi: 10.1007/s40618-019-01112-8
pii: 10.1007/s40618-019-01112-8
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
Nivolumab
31YO63LBSN
pembrolizumab
DPT0O3T46P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
337-345Références
Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723
doi: 10.1056/NEJMoa1003466
Wolchok JD, Neyns B, Linette G, Negrier S, Lutzky J, Thomas L, Waterfield W, Schadendorf D, Smylie M, Guthrie T Jr, Grob JJ, Chesney J, Chin K, Chen K, Hoos A, O’Day SJ, Lebbé C (2010) Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol 11:155–164
doi: 10.1016/S1470-2045(09)70334-1
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454
doi: 10.1056/NEJMoa1200690
Ribas A, Wolchok JD (2013) Combining cancer immunotherapy and targeted therapy. Curr Opin Immunol 25:291–296
doi: 10.1016/j.coi.2013.02.011
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373:23–34
doi: 10.1056/NEJMoa1504030
Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A, KEYNOTE-006 investigators (2015) Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372:2521–2532
doi: 10.1056/NEJMoa1503093
Postow MA, Callahan MK, Wolchok JD (2015) Immune checkpoint blockade in cancer therapy. J Clin Oncol 33:1974–1982
doi: 10.1200/JCO.2014.59.4358
Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A (2016) Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 387:1837–1846
doi: 10.1016/S0140-6736(16)00587-0
Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J, Curiel TJ, Colon-Otero G, Hamid O, Sanborn RE, O’Donnell PH, Drakaki A, Tan W, Kurland JF, Rebelatto MC, Jin X, Blake-Haskins JA, Gupta A, Segal NH (2016) Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol 34:3119–3125
doi: 10.1200/JCO.2016.67.9761
Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera OA, De Marinis F, Turna H, Lee JS, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR (2017) OAK Study Group (2017) Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 389:255–265
doi: 10.1016/S0140-6736(16)32517-X
Baxi S, Yang A, Gennarelli RL, Khan N, Wang Z, Boyce L, Korenstein D (2018) Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. BMJ. https://doi.org/10.1136/bmj.k793
doi: 10.1136/bmj.k793
pubmed: 29540345
pmcid: 5851471
Kumar V, Chaundary N, Garg M, Floudas CS, Soni P, Chandra AB (2017) Current diagnosis and management of immune related adverse events (irAEs) induced by immune checkpoint inhibitor therapy. Front Pharmacol. https://doi.org/10.3389/fphar.2017.0004
doi: 10.3389/fphar.2017.0004
pubmed: 28928657
pmcid: 5591978
Chang LS, Barroso-Sousa R, Tolaney SM, Hodi FS, Kaiser UB, Min L (2019) Endocrine toxicity of cancer immunotherapy targeting immune checkpoints. Endocr Rev 40:17–65
pubmed: 30184160
Cooper GS, Bynum ML, Somers EC (2009) Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun 33:197–207
doi: 10.1016/j.jaut.2009.09.008
Morganstein DL, Lai Z, Spain L, Diem S, Levine D, Mace C, Gore M, Larkin J (2017) Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma. Clin Endocrinol (Oxf) 86:614–620
doi: 10.1111/cen.13297
Scott ES, Long GV, Guminski A, Clifton-Bligh RJ, Menzies AM, Tsang VH (2018) The spectrum, incidence, kinetics and management of endocrinopathies with immune checkpoint inhibitors for metastatic melanoma. Eur J Endocrinol 178:175–182
doi: 10.1530/EJE-17-0810
Leonardi GC, Gainor JF, Altan M, Kravets S, Dahlberg SE, Gedmintas L, Azimi R, Rizvi H, Riess JW, Hellmann MD, Awad MM (2018) Safety of programmed death-1 pathway inhibitors among patients with non-small-cell lung cancer and preexisting autoimmune disorders. J Clin Oncol 36:1905–1912
doi: 10.1200/JCO.2017.77.0305
Danlos FX, Voisin AL, Dyevre V, Michot JM, Routier E, Taillade L, Champiat S, Aspeslagh S, Haroche J, Albiges L, Massard C, Girard N, Dalle S, Besse B, Laghouati S, Soria JC, Mateus C, Robert C, Lanoy E, Marabelle A, Lambotte O (2018) Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease. Eur J Cancer 91:21–29
doi: 10.1016/j.ejca.2017.12.008
Guaraldi F, La Selva R, Samà MT, D’Angelo V, Gori D, Fava P, Fierro MT, Savoia P, Arvat E (2018) 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. J Endocrinol Invest 41:549–556
doi: 10.1007/s40618-017-0772-1
Patel NM, Michelini VV, Snell JM, Balu S, Hoyle AP, Parker JS, Hayward MC, Eberhard DA, Salazar AH, McNeillie P, Xu J, Huettner CS, Koyama T, Utro F, Rhrissorrakrai K, Norel R, Bilal E, Royyuru A, Parida L, Earp HS, Grilley-Olson JE, Hayes DN, Harvey SJ, Sharpless NE, Kim WY (2018) Enhancing next-generation sequencing-guided cancer care through cognitive computing. Oncologist 23:179–185
doi: 10.1634/theoncologist.2017-0170
Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, Tolaney SM (2018) Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis. JAMA Oncol 4:173–182
doi: 10.1001/jamaoncol.2017.3064
Lee H, Hodi FS, Giobbie-Hurder A, Ott PA, Buchbinder EI, Haq R, Tolaney S, Barroso-Sousa R, Zhang K, Donahue H, Davis M, Gargano ME, Kelley KM, Carroll RS, Kaiser UB, Min L (2017) Characterization of thyroid disorders in patients receiving immune checkpoint inhibition therapy. Cancer Immunol Res 5:1133–1140
doi: 10.1158/2326-6066.CIR-17-0208
Gogas H, Ioannovich J, Dafni U, Stavropoulou-Giokas C, Frangia K, Tsoutsos D, Panagiotou P, Polyzos A, Papadopoulos O, Stratigos A, Markopoulos C, Bafaloukos D, Pectasides D, Fountzilas G, Kirkwood JM (2006) Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med 354:709–718
doi: 10.1056/NEJMoa053007
De Remigis A, de Gruijl TD, Uram JN, Tzou SC, Iwama S, Talor MV, Armstrong TD, Santegoets SJ, Slovin SF, Zheng L, Laheru DA, Jaffee EM, Gerritsen WR, van den Eertwegh AJ, Le DT, Caturegli P (2015) Development of thyroglobulin antibodies after GVAX immunotherapy is associated with prolonged survival. Int J Cancer 136:127–137
doi: 10.1002/ijc.28973
Shah RR, Shah DR (2019) Safety and tolerability of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in oncology. Drug Saf 42:181–198
doi: 10.1007/s40264-018-0772-x
Teulings HE, Limpens J, Jansen SN, Zwinderman AH, Reitsma JB, Spuls PI, Luiten RM (2015) Vitiligo-like depigmentation in patients with stage III-IV melanoma receiving immunotherapy and its association with survival: a systematic review and meta-analysis. J Clin Oncol 33:773–781
doi: 10.1200/JCO.2014.57.4756
Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA, National Comprehensive Cancer Network (2018) Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: american society of clinical oncology clinical practice guideline. J Clin Oncol 36:1714–1768
doi: 10.1200/JCO.2017.77.6385
Califano R, Lal R, Lewanski C, Nicolson MC, Ottensmeier CH, Popat S, Hodgson M, Postmus PE (2018) Patient selection for anti-PD-1/PD-L1 therapy in advanced non-small-cell lung cancer: implications for clinical practice. Future Oncol 14:2415–2431
doi: 10.2217/fon-2018-0330
Ruggeri RM, Campennì A, Giuffrida GP, Trimboli L, Giovanella F, Cannavò TS (2018) Endocrine and metabolic adverse effects of immune checkpoint inhibitors: an overview (what endocrinologists should know). J Endocrinol Invest. https://doi.org/10.1007/s40618-018-0984-z [EPub ahead of print]
doi: 10.1007/s40618-018-0984-z
pubmed: 30471004