PD-1 Blockade in Advanced Adrenocortical Carcinoma

Area of Science:

• Oncology
• Immunotherapy
• Genomics

Background:

• Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with limited therapeutic options.
• Evaluating the immunogenicity of ACC is crucial for developing novel treatment strategies.

Purpose of the Study:

• To assess the clinical activity and safety of pembrolizumab in patients with advanced ACC.
• To correlate treatment efficacy with tumor programmed death-ligand 1 (PD-L1) expression, microsatellite-high/mismatch repair deficient (MSI-H/MMR-D) status, and genomic factors.

Main Methods:

• A phase II clinical trial enrolled 39 patients with advanced ACC.
• Pembrolizumab (200 mg every 3 weeks) was administered without prior therapy restrictions.
• Objective response rate (ORR) was the primary endpoint, with efficacy correlated to biomarkers.

Main Results:

• The ORR to pembrolizumab was 23% (9 patients), with a disease control rate of 52%.
• Median progression-free survival was 2.1 months, and median overall survival was 24.9 months.
• Pembrolizumab demonstrated clinically meaningful and durable antitumor activity in microsatellite-stable ACC, with a manageable safety profile (13% grade 3/4 adverse events).

Conclusions:

• Pembrolizumab offers a viable treatment option for advanced ACC, particularly for microsatellite-stable tumors.
• The study identified a higher prevalence of MSI-H/MMR-D tumors in ACC than previously recognized.
• Biomarker status (PD-L1 expression, MSI-H/MMR-D) was not associated with objective response in this cohort.