Introduction: It has already been established that malignancies are capable of developing the capacity to evade immune surveillance through their utilisation of the body’s own immunomodulatory mechanisms – including immune checkpoints. These mechanisms, intended to prevent autoimmunity, have now been targeted with monoclonal antibody immunotherapies which aim to activate the immune system to recognise and eliminate malignant cells. The PD-1 immune checkpoint has been a particularly important target. However, a common side effect of immunotherapy is autoimmunity, commonly a thyroiditis. Recent literature has emerged to suggest that the development of these autoimmune sequalae may be associated with positive outcomes in cancer patients.
Method: Searches of PUBMED, MedLine, SCOPUS, CINAHL and Embase were undertaken in October 2019 and January 2020. Measures of median overall survival (MOS), progression free survival (PFS) and objective response rate (ORR) were extracted and pooled. A meta-analysis was conducted to compare the aforementioned parameters between immunotherapy patients who developed thyroid dysfunction, against those who did not.
Results: Eleven total retrospective and prospective cohort studies, with a total of 1423 patients, were included. The overall analysis demonstrated a statistically significant improvement for patients who developed thyroid dysfunction against those with normal thyroid dysfunction. These improvements were noted in the categories of overall survival (Hazard Ratio (HR) 0.40, 95% Confidence Interval (CI) 0.31 to 0.52), objective response rate percentage (ORR) (Thyroid dysfunction (ORR 37.20%, 95% CI 23.07 to 51.33) ; Non-thyroid dysfunction (ORR 11.23%, 95% CI 4.97 to 17.48), mean difference of progression free survival (mean difference=3.17 months, 95% CI 2.49 to 3.85) and progression free survival (HR 0.49, 95% CI 0.41 to 0.58).
Conclusions: From this Meta-analysis, there is a statistically significant association between overall survival, progression free survival and objective response rate, with the development of thyroid dysfunction in the setting of immune checkpoint inhibitor therapy.