Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study

Presotto, Elena Margherita; Rastrelli, Giulia; Desideri, Isacco; Scotti, Vieri; Gunnella, Susanna; Pimpinelli, Nicola; Vaccher, Emanuela; Bearz, Alessandra; Costanzo, F. Di; Bruggia, M.; Mini, Enrico; Maggi, Mario; Peri, Alessandro

doi:10.1007/s40618-019-01112-8

Cited by 35 publications

(27 citation statements)

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“…In our study, the median occurrence of endocrine disorders was 2 months, which agrees with the literature data [ 36 , 40 , 46 ]. In other studies, the median time of onset was estimated as ranging from 5.3 to 12 weeks [ 44 , 66 ]: hypothyroidism at 2.9 months and hyperthyroidism at 1.5 months [ 5 ].…”

Section: Discussionsupporting

confidence: 93%

Do endocrine adverse events predict longer progression-free survival among patients with non-small-cell lung cancer receiving nivolumab?

et al. 2021

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The aim of the study was to assess the occurrence and nature of immune-related endocrine adverse events (irAEs) among patients with non-small-cell lung cancer (NSCLC) treated with nivolumab. Methods: The study group included 35 patients (15 women, 20 men, 65.8 ± 7.1 years) with NSCLC in stage IIIB (n = 16, 45.7%) and IV (n = 19,54.3%) who were treated with nivolumab. Results: Of the studied patients, 34.3% (n = 12) developed endocrine irAEs (irAE group): 22.9% (n = 8) hyperthyroidism and 8.6% (n = 3) hypothyroidism, and in one case, hypophysitis was observed. The median irAEs onset time was 2 months. In the group of patients with thyroid disorders, permanent hypothyroidism eventually developed in 58.3%. The severity of the analyzed irAEs ranged from mild to moderate (Grade 1–2); the case of hypophysitis was estimated as Grade 3. The comparison of progression-free survival time (PFS) between the two groups showed longer PFS in patients in the irAE group (p = 0.021). Patients with irAE were treated significantly longer with nivolumab and they received more doses of nivolumab, however in Cox analysis we did not find patients with irAE to experience progression later than patients without them. Conclusions: Nivolumab therapy is associated with an increased risk of endocrine adverse effects, particularly thyroid dysfunction. Endocrine adverse effects can be successfully treated pharmacologically and usually do not require discontinuation of immunotherapy. The relationship between a better cancer prognosis in patients who developed endocrine irAE has not been found.

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Section: Discussionsupporting

confidence: 93%

Do endocrine adverse events predict longer progression-free survival among patients with non-small-cell lung cancer receiving nivolumab?

et al. 2021

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“…With regard to thyroid dysfunction, which is overall the most frequent endocrine irAE, both hypothyroidism or thyrotoxicosis may occur. The latter can be transient and can be followed by subsequent hypothyroidism [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Endocrine-related adverse events in a large series of cancer patients treated with anti-PD1 therapy

et al. 2021

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Purpose Immune checkpoint inhibitors have opened a new scenario in the treatment of cancer. These agents can elicit adverse events, which may affect different systems and organs, including the endocrine system. The aims of this study were to evaluate the impact of the anti-PD-1 molecules nivolumab and pembrolizumab on endocrine toxicity and on patient outcome. Methods A retrospective and multicentre study was designed, which involved a total of 251 patients affected by different tumors (mostly non-small cell lung cancer, 68.92% and melanoma, 24.30%) and treated with the PD-1 inhibitors nivolumab (61.35%) or pembrolizumab (38.65%) for up to 60 months. Clinical and biochemical data were recorded until July 31, 2020. Results Endocrine toxicity occurred in 70 out of 251 patients (27.89%). It was mostly related to thyroid dysfunction and in 75% of cases occurred within 6 months from the beginning of therapy. A previous endocrine morbidity and female gender were predictors of endocrine toxicity. There was no association between endocrine dysfunction and patient outcome. However, when all toxicities (i.e., endocrine and non endocrine) were considered, a significant association with progression-free survival and overall survival was found. Conclusions Thyroid alterations are frequently observed in cancer patients treated with anti PD-1 drugs, particularly in women and in the presence of a previous endocrinopathy. We suggest that regular thyroid assessment should be performed in these patients, especially in the first months of therapy. Finally, the onset of side effects, related to anti PD-1 agents, appears to be associated with a better outcome.

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“…The analysis of the problem is also complicated by the fact that Hashimoto’s disease affects approximately 4% of the general population and that thyroid antibodies are detected in 11% of healthy individuals [ 70 ]. However, an elevated level of thyroid antibodies found at the beginning of the treatment is a risk factor of both the development as well as exacerbation of thyroid disorders in the course of anti-PD-1 treatment [ 19 , 21 , 40 , 75 , 81 , 82 ]. In order to determine the potential differences in the pathogenesis of ICI and autoimmune thyroid disease, further investigations are needed [ 19 ].…”

Section: Thyroid Gland Disordersmentioning

confidence: 99%

Endocrine Adverse Events of Nivolumab in Non-Small Cell Lung Cancer Patients—Literature Review

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Wojas‐Krawczyk

et al. 2020

Cancers

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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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Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study

Cited by 35 publications

References 30 publications

Do endocrine adverse events predict longer progression-free survival among patients with non-small-cell lung cancer receiving nivolumab?

Do endocrine adverse events predict longer progression-free survival among patients with non-small-cell lung cancer receiving nivolumab?

Endocrine-related adverse events in a large series of cancer patients treated with anti-PD1 therapy

Endocrine Adverse Events of Nivolumab in Non-Small Cell Lung Cancer Patients—Literature Review

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