Lung cancer patients receiving immunotherapy develop thyroid dysfunction

In patients with non-small-cell lung cancer (NSCLC) treated with nivolumab, thyroid dysfunction may be a common development, according to a recent study in press with La Presse Médicale. In light of these results, screening these patients during treatment should be a requirement, concluded researchers

“Immunotherapy is a standard not only in second line but also in first line treatment in patients with [NSCLC] and other tumors…Studies have highlighted multisystemic adverse events linked to immunotherapies (gastrointestinal, cutaneous, respiratory, neurological, ocular). Multiple endocrine disorders have also been described…Thyroid disorders are second in terms of frequency, with an incidence of [2%] to 4%,” according to senior author Philippe Caron, MD, Centre Hospitalier Universitaire-Larrey, Cardiovascular and Metabolic Unit, Department of Endocrinology and Metabolic Diseases, Toulouse, France, and colleagues.

“Faced with the increasingly widespread use of anti-PD-1 monoclonal antibodies, it is important to study the incidence of thyroid disorders during anti-PD-1 therapy, and to establish diagnostic and therapeutic strategies,” they added.

In this retrospective study, Dr. Caron and colleagues assessed the incidence of thyroid dysfunction—including isolated thyrotoxicosis, biphasic thyroiditis, and hypothyroidism—in 105 patients with pre-treated, advanced NSCLC (median age: 61 years; 72 males) during their treatment with nivolumab, a PD-1 monoclonal antibody.

They defined these dysfunctions as follows:

• Isolated thyrotoxicosis: a transient or permanent TSH decrease of < 0.1 µU/mL, with no increases in TSH
• Biphasic thyroiditis: TSH decrease of < 0.1 µU/mL, and hypothyroidism with TSH levels increased above patient’s usual laboratory reference range
• Isolated hypothyroidism: a transient or permanent TSH increase above usual laboratory reference range (? 4 µU/mL), not preceded by a thyrotoxic phase

In all, 14.3% experienced a thyroid dysfunction. When researchers compared the nivolumab-treatment group with the control group, they found that thyroid dysfunction had developed in more females (53.3% vs 27.8%; P=0.07) and younger patients (median age: 56 years vs 62 years; P=0.02).

Thirteen patients developed thyrotoxicosis, with a median onset of 8 weeks, and five patients developed hypothyroidism. Researchers also noted that only two patients developed isolated hypothyroidism, which occurred relatively late into treatment (median: 30 weeks). Median time to onset of thyroid dysfunction was 1.8 months.

Anti-thyroid peroxidase antibodies were found in three patients, and immunotherapy was discontinued due to thyroid dysfunction in three patients.

Deaths occurred in 6.7% of patients with thyroid dysfunction compared with 33.3% of those in the control group, with a trend toward higher overall survival in patients who developed thyroid dysfunctions (HR: 0.16; 95% CI: 0.02-1.15; P=0.07).

“Immunotherapy is a turning point landmark in the treatment of various cancers. Given the expanding use of immunotherapy, even as a first-line treatment, oncologists will we increasingly faced with these endocrine toxicities. Thus, these adverse effects and particularly thyroid disorders deserve to be properly screened and treated. In the meantime, specific studies should be designed in order to understand the mechanisms implicated in their pathophysiology,” concluded Dr. Caron and colleagues.