Thyroid dysfunction is one of the most common adverse events that may occur during anti–PD‐1 immunotherapy.1 Now, a new study suggests that the phenomenon may be tied to longer overall survival and progression-free survival in patients with metastatic melanoma, non‐small cell lung carcinoma, and renal cell carcinoma.2 The authors also found a link between higher levels of antithyroid antibodies (ATAb) during treatment and improved overall survival and progression-free survival.
In the study, researchers looked at 168 patients with metastatic melanoma, non‐small cell lung carcinoma, and renal cell carcinoma who began anti–PD‐1 treatment — either nivolumab every 2 weeks or pembrolizumab every 3 weeks — between April 2016 and July 2017.
The researchers collected serum from patients prior to every time they administered treatment to measure their thyroid stimulating hormone (TSH) and free T4 levels. The researchers classified thyroid toxicity as “subclinical” when TSH levels were increased, in the case of subclinical hypothyroidism — or lowered, in the case of subclinical hyperthyroidism — and free T4 levels were normal. They classified thyroid toxicity as “overt” in the following way: when TSH levels were heightened and free T4 levels were lowered, it was designated as “overt hypothyroidism,” and when TSH levels were lowered and free T4 levels increased, it was designated as “overt hyperthyroidism.”
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The researchers measured antibodies directed against thyroid peroxidase (anti‐TPO) and thyroglobulin (anti‐Tg) using a Phadia 250 twice: at baseline and 2 months following the onset of treatment, or, if a patient died, the last sample that they had access to.
The investigators followed the patients for a median of 14.9 months. Of all patients, 20% (34 patients) developed subclinical thyroid dysfunction, and 12% (20 patients) developed overt thyroid dysfunction. Sixteen percent (27 patients) had preexisting thyroid dysfunction, a group that included 9 patients with hyperthyroidism and 18 patients with hypothyroidism. Of these 27 patients, 22 were categorized as having subclinical thyroid dysfunction based on THS values. Of all patients in the study, 48% (80 patients) did not develop thyroid dysfunction. The researchers were unable to establish thyroid dysfunction status in 7 patients “due to missing TSH values,” according to the paper.
Overall survival was higher among patients who developed overt thyroid dysfunction during treatment (hazard ratio [HR], 0.18; CI 95%, 0.04‐0.76, P =.020) compared with patients who did not have overt thyroid dysfunction — and so was progression-free survival (HR, 0.39; 0.15‐0.998; P =.050).
The 1-year overall survival rate among those who developed overt thyroid dysfunction during treatment was 94% compared with 59% among those who did not have overt thyroid dysfunction. One‐year progression-free survival rates were 64% and 34%, respectively.
There was no increase in survival linked to acquired subclinical thyroid dysfunction or preexisting thyroid dysfunction.
Patients with ATAb levels above the median at baseline did not have longer overall survival or progression-free survival. However, overall survival rates were higher for those who had ATAb levels that were above the median during treatment compared with those whose ATAb levels were below the median during treatment, at 83% vs 49%, respectively, at 1 year. Progression-free survival rates at 1 year were also higher for patients with above-the-median ATAb levels during treatment compared with levels below the median during treatment, at 54% vs 20%.
