Immunotherapy in pituitary carcinomas and aggressive pituitary tumors.

After temozolomide failure, no evidence-based treatment option is currently available for aggressive pituitary tumors (APTs) and pituitary carcinomas (PCs). Moreover, once temozolomide has failed, the survival of these patients is very poor. The use of immune-checkpoint inhibitors (ICIs) has been so far reported in a large cohort, a small phase 2 clinical trial, and in another five isolated cases (24 cases in total). Here, we review the available evidence on the efficacy and potential predictors of response to ICIs in PCs and APTs, namely the histological type (corticotroph versus lactotroph), the tumor type (PC versus APT), the presence of uncontrolled endogenous hypercortisolism, the type of protocol (combined ICIs versus monotherapy), programmed death-ligand 1 (PD-L1) expression, CD8+ cell infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and mismatch repair (MMR) status. We also discuss key clinical aspects that can already be implemented in the everyday practice and identify future research needs.