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

No effective therapies are available for patients with advanced adrenocortical carcinoma (ACC) progressing after standard therapy: EDP (etoposide, adriamycin, and 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.

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.

Cisplatin, 25 mg/m2 on day 1, and nivolumab, 240 mg on day 2, every 2 weeks, were administered to advanced/metastatic ACC with disease progression to EDP-M regimen plus/minus other chemotherapeutic regimens. The 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.

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. The median PFS was 4.3 months [95% CI, 3.9-13.0], and the 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 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria. One patient discontinued treatment after 1 cycle, due to grade 3 immune-related hepatitis.

The combination of 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.