Tumor PD-L1 expression and molecular profiling are not associated with immune checkpoint inhibitor-induced thyroid
Adi Horesh1, Rena Pollack1,2, Hovav Nechushtan1,3
1The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Abstract:
Background: Immune-checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC), however are frequently associated with thyroid immune-related adverse events (IRAEs). We investigated the association between patient characteristics, tumor PD-L1 expression and molecular profile with the development of thyroid IRAEs in NSCLC patients. Methods: Single center, retrospective study including 107 NSCLC patients treated with PD-1/PD-L1 inhibitors from April 2016 to July 2020. All patients were euthyroid at baseline with at least two TSH measurements post-treatment initiation. The primary outcome was the difference in tumor PD-L1 expression in patients who developed any thyroid IRAEs versus those who remained euthyroid. Additional outcomes included development of overt thyroid dysfunction, the association of specific molecular alterations with thyroid IRAEs, and onset of thyroid IRAEs as a function of tumor PD-L1 expression. Results: Overall, 37 (34.6%) patients developed any thyroid dysfunction and 18 (16.8%) developed overt thyroid dysfunction. Tumor PD-L1 staining intensity was not associated with thyroid IRAEs. TP53 mutation was less likely to be associated with any thyroid dysfunction (p < 0.05) and no association was found between EGFR, ROS, ALK or KRAS mutations. There was no association between PD-L1 expression and time to develop thyroid IRAEs. Conclusion: PD-L1 expression is not associated with the development of thyroid dysfunction in advanced NSCLC patients treated with ICIs, suggesting that thyroid IRAEs are unrelated to tumor PD-L1 expression.
Insights
Immune-checkpoint inhibitors (ICIs) can cause thyroid issues in non-small cell lung cancer (NSCLC) patients. This study found that tumor PD-L1 expression does not predict these thyroid immune-related adverse events (irAEs).
Area of Science:
- Oncology
- Immunology
- Endocrinology
Background:
- Immune-checkpoint inhibitors (ICIs) have transformed advanced non-small cell lung cancer (NSCLC) treatment.
- Thyroid immune-related adverse events (irAEs) are common complications of ICI therapy.
- Predictive biomarkers for thyroid irAEs in NSCLC patients remain largely unknown.
Purpose of the Study:
- To investigate the association between patient characteristics, tumor PD-L1 expression, and molecular profile with the development of thyroid irAEs in NSCLC patients treated with ICIs.
- To determine if tumor PD-L1 expression levels correlate with the incidence or timing of thyroid irAEs.
- To explore the relationship between specific genetic mutations and the occurrence of thyroid dysfunction.
Main Methods:
- Retrospective analysis of 107 advanced NSCLC patients treated with PD-1/PD-L1 inhibitors.
- Assessment of baseline thyroid function and monitoring of thyroid-stimulating hormone (TSH) levels post-treatment.
- Correlation of thyroid irAE development with tumor PD-L1 expression, TP53, EGFR, ROS, ALK, and KRAS mutations.
Main Results:
- Thyroid dysfunction occurred in 34.6% of patients, with 16.8% developing overt thyroid dysfunction.
- No significant association was found between tumor PD-L1 expression (staining intensity or level) and the development of any thyroid irAEs.
- TP53 mutations showed a trend towards being less likely associated with thyroid dysfunction (p < 0.05), while other tested mutations (EGFR, ROS, ALK, KRAS) showed no association.
Conclusions:
- Tumor PD-L1 expression is not a reliable predictor of thyroid irAEs in advanced NSCLC patients receiving ICIs.
- The development of thyroid irAEs appears to be independent of tumor PD-L1 expression levels.
- Further research is needed to identify predictive biomarkers for thyroid irAEs in ICI-treated NSCLC patients.
