Endocrine Adverse Events Related to Immune-Oncology Agents

Retrospective Experience of a Single Institution

Sofia España; Alejandra Pérez Montes de Oca; Montserrat Marques-Pamies; Marc Cucurull; Marta Domenech; José María Velarde; Isabel Salinas; Teresa Moran; Olatz Etxaniz


Transl Lung Cancer Res. 2020;9(1):103-110. 

In This Article

Abstract and Introduction


Background: Immune-oncology agents (IOA) represent a turning point in the treatment of several solid tumors (ST). Although their toxicity compares favorably with other treatments, IOA associate immune-related adverse events (IR-AE), among which endocrine-related AE stand out. We retrospectively evaluated the occurrence of endocrine (E) IR-AE in a cohort of patients with several ST treated with IOA. In addition, we assessed the correlation between likelihood of survival and the occurrence of IR-AE.

Methods: We collected data on clinical and molecular characteristics, efficacy and AE of 260 patients with ST treated with IOA from 2013 to 2017. We excluded patients with prior conditions or treatments potentially affecting thyroid test results.

Results: Lung cancer was the most prevalent diagnosis (70.2%). EIR-AE appeared in 18.1% of patients (total of 38 EIR-AE) and consisted of hypothyroidism, hyperthyroidism, pituitary disorders and type 1 diabetes mellitus in 60.5%, 21.1%, 15.8% and 2.6% of patients, respectively. EIR-AE were associated mainly to nivolumab, nivolumab plus ipilimumab (41.2% and 26.5%) and appeared after a median of 4.2 cycles of treatment. Specific therapy was required in 65.8% patients. There were significant differences in both progression-free survival (PFS) and overall survival (OS) for patients who experienced EIR-AE compared to those who did not [PFS: 56.7 (NC–NC) vs. 27.7 (14.3–41.3) months, P=0.008; OS: NC (NC–NC) vs. 31.4 (20.7–42.1) months, P=0.001].

Conclusions: The incidence of EIR-AE in our study is similar to other series. Patients who develop EIR-AE might have a better prognosis compared to those who do not experience them.


The advent of the immune-oncology agents (IOA) in the clinical scenario has been a relevant change in the therapeutic approach for several solid tumors (ST), including melanoma, non-small cell lung cancer (NSCLC) and urothelial tumors among others.[1,2] These IOA include anti CTLA-4 and anti-PD-1/PD-L1-based immunotherapy and have dramatically changed prognosis of these tumors, with a substantial improvement of overall survival (OS) and with a subset of patients presenting long-lasting responses.

Despite the significant survival benefit in these tumors, as well as an overall better toxicity profile compared to other systemic therapies, IOA present a new spectrum of toxicities. Overall, the boost of the immune system produced by these agents leads to an inflammatory environment in different body tissues, resembling autoimmune disorders, most commonly in the gastrointestinal tract and the skin.[3,4] Generally, the incidence of immune-related adverse events (IR-AE) is variable with a mild or moderate symptomatic burden at presentation. Usually, IR-AE can be well controlled with steroids, requiring dose delays and occasionally drug withhold.[4] However, IR-AE may be life-threatening with permanent disabling sequels. Their early recognition might help in taking relevant therapeutic measures, guaranteeing treatment adherence by reducing their severity and duration, as well as their impact in patients' quality of life.[5] In addition, the wide spectrum of toxicities related to IOA requires an interdisciplinary approach.[6]

Endocrine (E) IR-AE represent the most common form of IR-AE, being thyroid alterations the most prevalent.[2] For the present analysis, we sought to characterize the pattern of EIR-AE in a population of patients treated with IOA. We also aimed to correlate their appearance with survival. We hypothesized that EIA-AE occurrence could be associated to a better likelihood of survival in patients receiving IOA, independently of the tumor.