Thyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among cancer patients treated with anti-PD1 and anti-PDL1 monotherapies. We evaluated the clinical course and predictors of thyroid irAEs, in relation to outcomes of advanced cancer patients treated with combination anti-PD1/anti-CTLA4.
We conducted a territory-wide study and identified advanced cancer patients who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Thyroid function tests (TFTs) were monitored every three weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes.
One hundred and three patients were included (median age: 59 years; 71.8% men). About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n=4; subclinical, n=2), and 11 with hypothyroidism (overt, n=2; subclinical, n=9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (OR 3.67, 95% CI 1.19-11.4, p=0.024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was independently associated with better overall survival (adjusted hazard ratio 0.34, 95% CI 0.17-0.71, p=0.004).
Thyroid irAEs are common in routine clinical practice among advanced cancer patients treated with combination anti-PD1/anti-CTLA4, and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.