Thyroid disorders in programmed death 1 inhibitor-treated patients: Is previous therapy with tyrosine kinase inhibitors a predisposing factor?
Clin Endocrinol (Oxf)
; 92(3): 258-265, 2020 03.
Article
en En
| MEDLINE
| ID: mdl-31788837
ABSTRACT
BACKGROUND:
Programmed death 1 (PD-1) inhibitors are frequently associated with thyroid-related adverse events (TAEs), but many aspects remain unclear. This study aims to evaluate the incidence and characteristics of such events and to find any predictive factor for its development.METHODS:
We retrospectively analysed data from patients with advanced solid tumours (non-small-cell lung carcinoma, renal cell carcinoma, metastatic melanoma) treated with PD-1 inhibitors (nivolumab, pembrolizumab) in Oncology Unit B, Policlinico Umberto I of Rome, from June 2015 to December 2018. All patients underwent baseline thyroid function evaluations repeated monthly.RESULTS:
The cohort consisted of 126 patients (66.7% male, mean age 66.4 ± 9.7 years). One hundred and seven received nivolumab and 19 pembrolizumab. Twenty-three per cent of patients experienced TAEs (mainly CTCAE grade 1), with hypothyroidism in 15.1% (subclinical 11.9%, overt 3.2%) and hyperthyroidism in 8.0% (subclinical 4.8%, overt 3.2%). Median time to TAE onset was 8.7 ± 6.8 weeks (10.4 ± 7.6 weeks for hypothyroidism, 5.4 ± 3.0 weeks for hyperthyroidism). Most TAEs (89.7%) appeared within the first 3 months, none after 8 months. Most hypothyroid patients (63.2%) had previously been treated with a tyrosine kinase inhibitor (TKI). Logistic regression analysis showed that pretreatment with a TKI was a major predisposing factor for the development of hypothyroidism (OR 9.2, 95% CI 1.4-59.9, P = .020).CONCLUSIONS:
TAEs are common during anti-PD-1 therapy and usually occur within the first 3 months of treatment. This is the first study evaluating the impact of previous oncologic therapies on TAEs, identifying TKI as a major risk factor for the development of hypothyroidism in patients treated with anti-PD-1.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades de la Tiroides
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Inhibidores de Proteínas Quinasas
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Endocrinol (Oxf)
Año:
2020
Tipo del documento:
Article
País de afiliación:
Italia