Immunotherapy for endocrine tumours: a clinician's perspective

Area of Science:

• Oncology
• Endocrinology
• Immunology

Background:

• Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has transformed cancer treatment but has limited application in endocrine tumors.
• ICIs are typically reserved for advanced or refractory endocrine malignancies after conventional therapies have failed.

Purpose of the Study:

• To review the current efficacy of immunotherapy, specifically ICIs, in various endocrine tumors.
• To identify potential predictive biomarkers for immunotherapy response in endocrine cancers.

Main Methods:

• Systematic review of studies evaluating ICIs in adrenocortical carcinoma, phaeochromocytoma/paraganglioma, thyroid carcinomas, and neuroendocrine tumors.
• Analysis of response rates and discussion of factors influencing efficacy, including tumor type, mutation burden, and PD-L1 expression.

Main Results:

• Variable response rates observed across endocrine tumors: adrenocortical carcinoma (14-23%), phaeochromocytoma/paraganglioma (9%), differentiated thyroid carcinoma (9%), medullary thyroid cancer (low, except high TMB), anaplastic thyroid cancer (better with high TMB/PD-L1), parathyroid carcinoma (limited), pituitary carcinoma (potentially favorable), and advanced neuroendocrine tumors (15%).
• Combinations of ICIs with tyrosine kinase inhibitors showed higher efficacy in differentiated thyroid carcinomas.
• High tumor mutation burden (TMB) and PD-L1 expression appear to predict better response in anaplastic thyroid cancer.

Conclusions:

• Immunotherapy with ICIs demonstrates limited but variable efficacy in endocrine tumors, necessitating further investigation.
• Biomarkers such as programmed death 1/programmed death ligand 1 (PD-1/PD-L1) and TMB require evaluation as predictors of response.
• Randomized prospective studies are essential to establish robust data on ICI efficacy and safety in endocrine oncology.