Combination immunotherapy with ipilimumab and nivolumab in patients with advanced adrenocortical carcinoma: a subgroup analysis of CA209-538

Oncoimmunology. 2021 Apr 12;10(1):1908771. doi: 10.1080/2162402X.2021.1908771.

Abstract

Background: Adrenocortical carcinoma is a rare malignancy, with poor prognosis and limited treatment options for patients with advanced disease. Chemotherapy is the current standard first-line treatment, providing only a modest survival benefit. There is only limited treatment experience with immunotherapy using single-agent anti-PD-1/PD-L1 therapy. To date no clinical trials have been reported using combination immunotherapy with anti-CTLA-4 and anti-PD-1 blockade in this patient population. Methods: CA209-538 is a prospective multicentre clinical trial in patients with advanced rare cancers. Participants received the anti-PD-1 antibody nivolumab (3 mg/kg IV) and the anti-CTLA-4 antibody ipilimumab (1 mg/kg IV) every three weeks for four doses, followed by nivolumab (3 mg/kg IV) every two weeks and continued for up to 96 weeks, until disease progression or unacceptable toxicity. Response was assessed every 12 weeks by RECIST version 1.1. Primary endpoint was clinical benefit rate (complete response, partial response, stable disease at 12 weeks). Results: Six patients with adrenocortical carcinoma were enrolled and received treatment. Two patients (33%) have an ongoing partial response (10 and 25 months +) and two patients (33%) stable disease leading to a disease control rate of 66%. Both responders had tumors with a microsatellite instable phenotype. One patient rapidly progressed shortly after enrollment into the trial and did not undergo restaging. Immunotherapy-related toxicity was reported in all patients, with four patients (67%) experiencing grade 3/4 hepatitis leading to discontinuation of treatment. Conclusions: This is the first treatment experience using ipilimumab and nivolumab combination immunotherapy in patients with advanced adrenocortical carcinoma. Durable responses have been observed in a subset of patients suggesting that this treatment regimen should be further investigated in this patient population.

Keywords: Adrenocortical carcinoma; anti-ctla-4; anti-pd-1; anti-pd-l1; ipilimumab; nivolumab.

Publication types

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

MeSH terms

  • Adrenal Cortex Neoplasms* / drug therapy
  • Adrenocortical Carcinoma* / drug therapy
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Humans
  • Immunotherapy / adverse effects
  • Ipilimumab / toxicity
  • Nivolumab / toxicity
  • Prospective Studies

Substances

  • Ipilimumab
  • Nivolumab

Grants and funding

The study received funding and drug support from Bristol–Myers Squibb, funding support was also provided in part by a grant from the Commonwealth of Australia, Dept. Health Accelerated Research Program. A Behren is supported by a fellowship from the Department of Health and Human Services acting through the Victorian Cancer Agency; Bristol-Myers Squibb; Commonwealth of Australia, Dept. Health Accelerated Research Program; Victorian Cancer Agency.