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

Publication date: Available online 21 June 2018
Source:Seminars in Oncology
Author(s): R.T. Casey, O. Giger, I. Seetho, A. Marker, D. Pitfield, L.H. Boyle, M. Gurnell, A. Shaw, M. Tischowitz, E.R. Maher, V.K. Chatterjee, T. Janowitz, G. Mells, P. Corrie, B.G. Challis
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 who presented with severe Cushing's syndrome 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 twelve weeks and 2 cycles of pembrolizumab administration revealed significant disease progression and treatment was discontinued. Seven weeks later, the patient became jaundiced and died rapidly with fulminant liver failure.Conclusion: Treatment of MMR-deficient cortisol-secreting ACC with pembrolizumab may be ineffective due to supra-physiological levels of circulating corticosteroids, which may in turn mask severe drug-induced organ damage.



https://ift.tt/2Kd33kx