MON-502 Evaluating the Response of Immunotherapy in Metastatic Adrenocortical Carcinoma - A Single Institution Retrospective Review

Abstract Disclosure: K.I. Wolf: None. E.A. Hesseltine: None. Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a 5-year relative metastatic survival rate of 5.7%. Surgical resection remains the only potential curative treatment, with chemotherapy and radiation providing variable benefits. In the last several years, clinical trials have investigated the outcome of immune checkpoint inhibitors (ICI) in this population. Our objective was to evaluate the response of patients with metastatic ACC undergoing immunotherapy at a single institution between 2020-2024 using RECIST 1.1 best overall response in a retrospective review. Twenty-four patients (8M, 16F) with metastatic ACC received pembrolizumab. The mean age of diagnosis was 45.4 years. Fourteen (58%) were deceased at time of review. The majority (16, 67%) had evidence of glucocorticoid excess. Of the 18 patients who underwent a surgical procedure, four (22%) were post neoadjuvant therapy. Median tumor size was 10.5 cm, and most patients (15, 83%) had high grade disease via Ki-67 index. Other treatment modalities included mitotane (16, 67%), cytotoxic chemotherapy (21, 87%), and radiation (15, 63%) to either the surgical bed or sites of distant metastases. Pembrolizumab was the initial systemic treatment modality in 9 (38%) patients and followed disease progression as second- and third-line agents in 13 (54%) and 2 (8%) patients, respectively. Two (8%) patients reached completion of a 2-year trial with complete responses. Of the remaining 22 patients, 6 (27%) are actively on therapy (4 mixed response, 2 PD thus far), and 16 (73%) ceased ICI secondary to hospice enrollment (9), functional performance decline (1), or PD (6). The overall response rate (ORR) was 9%, which mirrors clinical trial data (6-25%). Two patients have had continued, long-term, CR for several years, which has never been seen with other treatment modalities in this population and further investigation is needed to determine the responders. The high percentage of patients with glucocorticoid excess and singular patient with a germline mutation in DNA mismatch repair genes may have played a role in lowering the overall response rate. Further research is necessary to evaluate the clinical characteristics of a mixed response to immunotherapy and determine the impact, if any, on the order of treatment (with respect to cytotoxic chemotherapy and immunotherapy) and combination immunotherapy, which has proven highly effective in other solid tumors. Presentation: Monday, July 14, 2025