Abstract
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. For stage I
and II tumors, surgery is a curative option, but even in these cases recurrence
is frequent. Practical guidelines advocate a combination of mitotane with
etoposide, doxorubicin, and cisplatin as first-line therapy for metastatic
adrenocortical carcinoma. However, this scheme presents limited efficacy and
high toxicity. The use of Immune Checkpoint Inhibitors (ICI) and multi-Tyrosine
Kinase Inhibitors (mTKI) has modified the approach of multiple malignancies. The
expectation of their applicability on advanced adrenocortical carcinoma is high
but the role of these new therapies persists unclear. This article provides a
short summary of last years’ findings targeting outcomes, limitations,
and adverse effects of these new therapeutic approaches. The results of recent
trials and case series pointed pembrolizumab as the most promising drug among
these new therapies. It is the most often used ICI and the one presenting the
best results with less related adverse effects when in comparison to the
standard treatment with mitotane. Hereafter, the identification of specific
molecular biomarkers or immune profiles associated with ICI or mTKI good
response will facilitate the selection of candidates for these therapies. So
far, microsatellite instability and Lynch Syndrome related germline mutations
are suggested as predictive biomarkers of good response. Contrarywise, cortisol
secretion has been associated with more aggressive ACC tumors and potentially
poor responses to immunotherapy.
Key words
immune checkpoint inhibitors - multi-tyrosine kinase inhibitors - immunotherapy - mitotane
