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Multicenter Study
. 2021 Oct;74(1):172-179.
doi: 10.1007/s12020-021-02750-w. Epub 2021 May 25.

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

Rossella Rubino  1 , Andrea Marini  2 , Giandomenico Roviello  2 , Elena Margherita Presotto  1 , Isacco Desideri  3 , Isabella Ciardetti  4 , Marco Brugia  5 , Nicola Pimpinelli  4 , Lorenzo Antonuzzo  5   6 , Enrico Mini  2 , Lorenzo Livi  3 , Mario Maggi  1 , Alessandro Peri  7
Affiliations
Multicenter Study

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

Rossella Rubino et al. Endocrine. 2021 Oct.

Abstract

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.

Keywords: Anti PD-1; Cancer; Endocrine toxicity; Immunotherapy.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Time of onset of endocrine toxicity. The % refers to the total number of patients in which endocrine toxicity was found (n = 70)
Fig. 2
Fig. 2
Association between endocrine toxicity and clinical outcomes. Kaplan–Meier plots of (A) progression-free survival (PFS) and (B) overall survival (OS) in patients who developed endocrine toxicity vs patients who did not
Fig. 3
Fig. 3
Association between all toxicities and clinical outcomes. Kaplan–Meier plots of (A) progression-free survival (PFS) and (B) overall survival (OS) in patients who developed toxicities vs patients who did not
See this image and copyright information in PMC

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