Nivolumab in Metastatic Adrenocortical Carcinoma: Results of a Phase 2 Trial

J Clin Endocrinol Metab. 2019 Dec 1;104(12):6193-6200. doi: 10.1210/jc.2019-00600.


Context: Systemic treatment of metastatic adrenocortical carcinoma (ACC) remains limited to chemotherapy and mitotane. Preliminary evidence suggesting that antitumor immune responses can be elicited in ACC has fostered interest in checkpoint inhibitors such as anti-PD-1 nivolumab.

Objective: The primary endpoint was objective response rate according to the response evaluation criteria in solid tumors. Secondary endpoints were progression-free survival (PFS), overall survival, and safety.

Design: Single-arm, multicenter, phase 2 clinical trial with two-stage design.

Setting: Comprehensive cancer center.

Patients: Ten adult patients with metastatic ACC previously treated with platinum-based chemotherapy and/or mitotane as well as patients who declined front-line chemotherapy.

Intervention: Nivolumab (240 mg) IV every 2 weeks.

Results: Ten patients with metastatic ACC were enrolled between March and December 2016. The median number of doses of nivolumab administered was two. Three patients only received one treatment [one died of disease progression, one discontinued due to adverse events (AEs), one withdrew after beginning treatment]. The median PFS was 1.8 months. The median follow-up was 4.5 months (range, 0.1 to 25.6 months). Two patients had stable disease for a duration of 48 and 11 weeks, respectively. One patient had an unconfirmed partial response but discontinued the study due to an AE. Most AEs were grade 1/2. The most common grade 3/4 treatment-related AEs were aspartate aminotransferase and alanine aminotransferase elevations, mucositis, and odynophagia.

Conclusion: Nivolumab demonstrated modest antitumor activity in patients with advanced ACC. The nivolumab safety profile was consistent with previous clinical experience without any unexpected AEs in this population.

Trial registration: NCT02720484.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / drug therapy*
  • Adrenal Cortex Neoplasms / pathology
  • Adrenocortical Carcinoma / drug therapy*
  • Adrenocortical Carcinoma / secondary
  • Adult
  • Aged
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Nivolumab / therapeutic use*
  • Prognosis
  • Survival Rate


  • Antineoplastic Agents, Immunological
  • Nivolumab

Associated data