Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab

Casey, R. T., Giger, O., Seetho, I., Marker, A., Pitfield, D., Boyle, L. H., Gurnell, M., Shaw, A., Tischowitz, M., Maher, E. R., Chatterjee, V. K., Janowitz, T., Mells, G., Corrie, P., Challis, B. G. (June 2018) Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab. Semin Oncol. ISSN 0093-7754

URL: https://www.ncbi.nlm.nih.gov/pubmed/30262398
DOI: 10.1053/j.seminoncol.2018.06.001

Abstract

CONTEXT: Metastatic adrenocortical carcinoma (ACC) is an aggressive malignancy with a poor prognosis and limited therapeutic options. A subset of ACC is due to Lynch syndrome, an inherited tumor syndrome resulting from germline mutations in mismatch repair (MMR) genes. It has been demonstrated that several cancers characterized by MMR deficiency are sensitive to immune checkpoint inhibitors that target PD-1. Here, we provide the first report of PD-1 blockade with pembrolizumab in a patient with Lynch syndrome and progressive cortisol-secreting metastatic ACC. CASE REPORT: A 58-year-old female with known Lynch syndrome presented with severe Cushing's syndrome and was diagnosed with a cortisol-secreting ACC. Three months following surgical resection and adjuvant mitotane therapy the patient developed metastatic disease and persistent hypercortisolemia. She commenced pembrolizumab, but her second cycle was delayed due to a transient transaminitis. Computed tomography performed after 12 weeks and 2 cycles of pembrolizumab administration revealed significant disease progression and treatment was discontinued. After 7 weeks, the patient became jaundiced and soon died due to fulminant liver failure. CONCLUSION: Treatment of MMR-deficient cortisol-secreting ACC with pembrolizumab may be ineffective due to supraphysiological levels of circulating corticosteroids, which may in turn mask severe drug-induced organ damage.

Item Type: Paper
Subjects: diseases & disorders > cancer
CSHL Authors:
Highlight: Janowitz, Tobias
Depositing User: Matthew Dunn
Date: 21 June 2018
Date Deposited: 10 Oct 2018 18:35
Last Modified: 10 Oct 2018 18:35
Related URLs:
URI: http://repository.cshl.edu/id/eprint/37222

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