Endocrine Toxicity and Outcomes in Patients With Metastatic Malignancies Treated With Immune Checkpoint Inhibitors.

CONTEXT

Immune checkpoint inhibitors (ICIs) have gained a revolutionary role in management of many advanced malignancies. However, immune-related endocrine events (irEEs), have been associated with their use. irEEs have nonspecific clinical presentations and variable timelines, making their early diagnosis challenging.

OBJECTIVE

To identify risk factors, timelines, and prognosis associated with irEEs development.

DESIGN AND SETTING

Retrospective observational study within the Cleveland Clinic center.

PATIENTS

Metastatic cancer adult patients who received ICIs were included.

METHODS

570 charts were reviewed to obtain information on demographics, ICIs used, endocrine toxicities, cancer response to treatment with ICI, and overall survival.

MAIN OUTCOME MEASURES

Incidence of irEEs, time to irEEs development and overall survival of patients who develop irEEs.

RESULTS

The final cohort included 551 patients. The median time for the diagnosis of irEEs was 9 weeks. Melanoma was associated with the highest risk for irEEs (31.3%). Ipilimumab appeared to have the highest percentage of irEEs (29.4%), including the highest risk of pituitary insufficiency (11.7%), the most severe (Grade 4 in 60%) and irreversible (100%) forms of irEEs. Forty-five percent of patients with irEEs had adequate cancer response to ICI compared to 28.3% of patients without irEEs ( = 0.002). Patients with irEEs had significantly better survival compared to patients without irEEs ( < 0.001).

CONCLUSIONS

In the adult population with metastatic cancer receiving treatment with ICI, irEEs development may predict tumor response to immunotherapy and a favorable prognosis. Ipilimumab use, combination ICI therapy, and melanoma are associated with a higher incidence of irEEs.