Chemo-immunotherapy with cisplatin and nivolumab as second line approach in metastatic adrenocortical carcinoma

Context No effective therapies are available for patients with advanced adrenocortical carcinoma (ACC) progressing after standard therapy: EDP (etoposide, adriamycin, cisplatin) and mitotane (EDP-M regimen). These patients have poor prognosis with a median life expectancy of 6-7 months. Immunotherapy in this setting is promising. Concomitant chemotherapy administration can enhance the efficacy of immunotherapy, as demonstrated in other malignancies. Objective This retrospective study aims to explore the activity of a combination of cisplatin and nivolumab administered to patients with ACC who have previously undergone chemotherapy and mitotane treatment. Patients and methods Cisplatin, 25 mg/m2 on day 1 and nivolumab 240 mg on day 2, every two weeks, were administered to advanced/metastatic ACC with disease progression to EDP-M regimen plus/minus other chemotherapeutic regimens. Primary endpoint was the disease response according to RECIST. Secondary endpoints were clinical benefit, disease control rate (DCR), overall survival (OS), progression free survival (PFS), and safety. Results Twenty-three patients were enrolled between January 2023 and March 2025. The median follow-up was 15.1 months. Eight patients (34.8% [95% CI, 15.3-54.2%]) obtained a partial response and 4 patients (17.3%) a stable disease, therefore 12 patients (52.2%) obtained a clinical benefit. The DCR after 6 months was obtained in 39.1% [95%CI, 19.7-61.5%] of patients. Median PFS was 4.3 months [95% CI, 3.9-13.0] and median OS was 18.9 months [95% CI, 15.8-not reached]. Chemo-immunotherapy combination was well-tolerated, and most toxicities were limited to grade G1-2 according to NCI-CTCAE criteria. One patient discontinued treatment after 1 cycle, due to grade 3 immune-related hepatitis. Conclusion Cisplatin and nivolumab is an active regimen in advanced, previously treated, ACC patients. The long survival achieved in this patient population with a poor prognosis is promising.