Endocrine Abstracts

Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a 5-year relative survival rate of 5.7% for those with metastatic disease. 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.

Objective/Methods: Evaluate the response of patients with metastatic ACC undergoing immunotherapy at a single institution between 2020-2024 using RECIST best overall response in a retrospective review.

Results: Twenty-two patients (8M, 14F) with metastatic ACC received pembrolizumab. With respect to various treatment modalities, 16 patients (4-post neoadjuvant therapy) underwent surgical resection (14 high-grade disease via Ki-67 index), 15 patients received mitotane, 19 patients underwent cytotoxic chemotherapy, and 14 patients had either adjuvant radiation to the surgical bed or sites of distant metastases. Pembrolizumab was the initial systemic treatment modality in 9 patients and followed disease progression as second- and third-line agents in 11 and 2 patients, respectively. Two patients reached completion of a 2-year trial with either complete response (1) (CR) or partial response (1) (PR). Of the remaining 20 patients, 1 has not completed initial imaging post-therapy, 4 are actively on therapy (1 stable disease (SD), 3 thus far PD), and 15 patients ceased ICI secondary to hospice enrollment (8), functional performance decline (1), or PD (6).

Discussion: The overall response rate (ORR) was 10%, which is in line with published clinical trials that have investigated immunotherapy in patients with metastatic ACC (6-25%). However, RECIST does not capture heterogenous responses. The identification of a singular new lesion qualifies for PD, even when other target lesions may have CR/PR, which skews the results in favor of progression. Nonetheless, a continued long-term response has never been seen with other treatment modalities and therefore, further research is necessary to evaluate the clinical characteristics of a mixed response to immunotherapy, as has been done in other solid organ tumors, and determine the impact, if any, in the order of treatment with respect to cytotoxic chemotherapy and immunotherapy.