MON-304 - Thyroid Immune-Related Adverse Effects within 1 Year of PD-1 and PD-L1 Inhibitor Initiation and Its Effects on Outcomes of Patients with Lung Cancer

Thyroid immune-related adverse effects (irAE) are one of the most frequently encountered endocrine toxicities associated with PD-1 and PD-L1 immune checkpoint inhibitors used in lung cancer therapy. Prior studies suggest that endocrine irAE may be associated with improved survival, suggesting that these toxicities may reflect heightened antitumor immune activity rather than isolated complications. In this study, we evaluate thyroid dysfunction during the first year of PD-1/PD-L1 inhibitor therapy and examine its relationship with treatment response and survival, to better inform prognostic assessment and clinical management.

A retrospective cohort study was conducted using data from TriNetX Research Network. At the time of analysis, this included 152, 775, 371 patients across 112 healthcare organizations. We identified patients with lung cancer who were treated with the four most common PD-1/PD-L1 inhibitors, namely pembrolizumab, nivolumab, atezolizumab, and durvalumab, and subsequently developed thyroid disease since immunotherapy initiation, specifically thyroiditis, hyperthyroidism, and hypothyroidism. Kaplan-Meier analysis assessed overall survival. Statistical comparisons of survival rates between groups were performed using the log-rank test. Propensity matching was used to adjust for age, sex, comorbidities, and lines of treatment.

Among the patients, 35,267 are on pembrolizumab, 13,617 on nivolumab, 10,113 on durvalumab, and 9,462 on atezolizumab. There was significantly improved overall survival for those who developed hypothyroidism on pembrolizumab (721 days vs 426 days, p < 0.0001), nivolumab (668 days vs 325 days, p < 0.0001), and atezolizumab (439 days vs 330 days, p = 0.0005). There was also significantly improved overall survival for those who developed hyperthyroidism on pembrolizumab (755 days vs 444 days, p < 0.0001), nivolumab (620 days vs 300 days, p < 0.0001), and atezolizumab (462 days vs 302 days, p = 0.0096). Patients on durvalumab who developed hypothyroidism or hyperthyroidism had no difference in survival. There was significantly improved overall survival for those who developed thyroiditis on pembrolizumab (844 days vs 433 days, p < 0.0001), nivolumab (823 days vs 362 days, p < 0.0001), and durvalumab (1,844 days vs 859 days, p < 0.0001). Patients on atezolizumab who developed thyroiditis had no difference in survival.

Across PD-1/PD-L1 inhibitors, the development of thyroid irAEs was consistently associated with prolonged overall survival compared with matched patients without thyroid irAEs. Survival differences ranged from 300 to 1,000 days depending on agent and thyroid phenotype, mirroring prior reports linking endocrine irAEs with improved immunotherapy outcomes. The magnitude of benefit supports the concept that thyroid irAEs reflect systemic immune activation rather than isolated treatment toxicity.

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