Corticotropic insufficiency in a monocentric prospective cohort of patients with lung cancer treated with nivolumab: Prevalence and etiology

Abstract

Introduction: Cancer therapy has greatly progressed in the past few years, due to development of immune checkpoint proteins. These immunotherapies, when applied to eligible patients, have significantly reduced mortality but are prone to induce immune side-effects, including pituitary disorder and low adreno-corticotropic hormone (ACTH) and cortisol levels. We aimed to assess the prevalence and etiology of corticotropic insufficiency through a systematic screening of cortisol and ACTH levels in patients with lung cancer treated with nivolumab perfusion.

Material and methods: All patients from our Center with indications for nivolumab treatment for pulmonary squamous cell carcinoma or adenocarcinoma resistant to chemotherapy were successively included and underwent cortisol and ACTH assay before each nivolumab perfusion. When cortisol was below normal without ACTH elevation, we screened for pituitary metastasis, hypophysitis or corticosteroid treatment that could explain the corticotropic insufficiency.

Results: Data from 75 patients (80.0% men, 20.0% women) showed 10.7% asymptomatic corticotropic insufficiency, with a mean cortisol level of 2.76±1.27μg/dl. Diagnosis was made during the first 2 months of nivolumab treatment in 88% of cases. Corticosteroid treatment explained the low cortisol level in 25.0% of cases. No pituitary metastases were found. Hypophysitis was suspected in 75.0% of cases.

Conclusion: In a 75-patient cohort with non-small cell lung cancer treated with the PD1 antibody nivolumab and systematically screened for cortisol abnormalities, 10.7% of patients showed asymptomatic corticotropic insufficiency. Excluding corticotropic insufficiency secondary to corticosteroid treatment, 8.0% of patients presented cortisol level<5μg/dl attributed to hypophysitis. Cortisol screening enables hydrocortisone replacement treatment to be prescribed if necessary, preventing risk of adrenal crisis.

Keywords: Cancer pulmonaire; Corticotropic insufficiency; Effet indésirable; Immunotherapy; Immunothérapie; Insuffisance corticotrope; Lung cancer; Nivolumab; Side effect.