Efficacy of Treatment With PARP Inhibitor and Immunotherapy for Aggressive Adrenocortical Carcinomawith Cushing’s Syndrome Refractory to Treatment With EDP Chemotherapy and Mitotane

A 39-year-old female with a past medical history of Ehlers-Danlos syndrome, Celiac disease, Hashimoto’s hypothyroidism and germline BRCA mutation presented with abdominal pain and distension. CT imaging demonstrated innumerable bilateral pulmonary nodules concerning for metastases, paraoesophageal adenopathy, multiple right adrenal masses, left adnexal cyst, and a small sclerotic lesion within the right iliac bone. CT guided biopsy of a 6 cm right adrenal mass revealed high grade carcinoma with areas of necrosis, and tumor markers were positive for synaptophysin, Melan-A and inhibin but negative for TTF1 and CK7, HMB45 and S100. A diagnosis of stage IV adrenocortical carcinoma was made and, at the time of diagnosis, a 24-hour urinary cortisol was elevated at 791.4 mcg (nl<45.0 mcg). Surgery was deferred given widespread metastatic disease. She initially completed 4 cycles of chemotherapy with EDP-Mitotane along with Metyrapone to normalize her urine cortisol. Subsequent restaging CT imaging revealed a mixed response to chemotherapy with new focal sclerotic areas in the left fifth rib concerning for new metastases. Due to suboptimal initial therapeutic response, less traditional treatment options were explored. PARP inhibitor and immunotherapy were considered, and she received Rucaparib followed by two cycles of Ipilimumab and Nivolumab, resulting in a limited response and complicated by reversible myocarditis likely due to immunotherapy. Further restaging CT imaging demonstrated disease progression, and patient then completed one month of Cisplatin and Etoposide and palliative radiation to the right adrenal tumor all while continuing Mitotane and Metyrapone. Her most recent restaging CT images indicated further disease progression. She was then transitioned to Sorafenib, Mebendazole, and Sulindac daily for CTNNB1 mutation with plans to rechallenge with a different PARP inhibitor (Olaparib) for BRCA1 mutation. Most recently, patient has self-discontinued Mitotane due to intolerable side effects. In conclusion, a highly aggressive adrenocortical carcinoma associated with Cushing’s syndrome was treated with PARP inhibitor and immunotherapy, after initial failure with a traditional EDP+Mitotane regimen, with limited benefit. References: 1. Berruti A, Terzolo M, Sperone P, et al. Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer. 2005;12(3):657–666. doi:10.1677/erc.1.010252. 2. Mohan DR, Lerario AM, Hammer GD. Therapeutic Targets for Adrenocortical Carcinoma in the Genomics Era. J Endocr Soc. 2018;2(11):1259–1274. Published 2018 Sep 26. doi:10.1210/js.2018-00197