Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial

We assessed the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with previously treated metastatic adrenocortical carcinoma (mACC).

In this phase 1b expansion cohort, patients with mACC and prior platinum-based therapy received avelumab at 10 mg/kg intravenously every 2 weeks. Continuation of mitotane was permitted; however, mitotane levels during the study were not recorded. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors v1.1.

Fifty patients received avelumab and were followed for a median of 16.5 months. Prior treatment included ≥2 lines in 74.0%; mitotane was continued in 50.0%. The objective response rate (ORR) was 6.0% (95% CI, 1.3% to 16.5%; partial response in 3 patients). Twenty-one patients (42.0%) had stable disease as best response (disease control rate, 48.0%). Median progression-free survival was 2.6 months (95% CI, 1.4 to 4.0), median overall survival (OS) was 10.6 months (95% CI, 7.4 to 15.0), and the 1-year OS rate was 43.4% (95% CI, 27.9% to 57.9%). In evaluable patients with PD-L1+ (n = 12) or PD-L1- (n = 30) tumors (≥5% tumor cell cutoff), ORR was 16.7% vs 3.3% (P = .192). Treatment-related adverse events (TRAEs) occurred in 82.0%; the most common were nausea (20.0%), fatigue (18.0%), hypothyroidism (14.0%), and pyrexia (14.0%). Grade 3 TRAEs occurred in 16.0%; no grade 4 to 5 TRAEs occurred. Twelve patients (24.0%) had an immune-related TRAE of any grade, which were grade 3 in 2 patients (4.0%): adrenal insufficiency (n = 1), and pneumonitis (n = 1).

Avelumab showed clinical activity and a manageable safety profile in patients with platinum-treated mACC.

Clinicaltrials.gov NCT01772004 ; registered January 21, 2013.

Journal for immunotherapy of cancer. 2018 Oct 22*** epublish ***

Christophe Le Tourneau, Christopher Hoimes, Corrine Zarwan, Deborah J Wong, Sebastian Bauer, Rainer Claus, Martin Wermke, Subramanian Hariharan, Anja von Heydebreck, Vijay Kasturi, Vikram Chand, James L Gulley

Department of Medical Oncology, Institut Curie, 26, rue d'ulm, 75005, Paris & Saint-Cloud, France. ., Case Western Reserve University and University Hospitals Seidman Cancer Center, Cleveland, OH, USA., Lahey Hospital and Medical Center, Burlington, MA, USA., UCLA Department of Medicine, California, Los Angeles, USA., Department of Medical Oncology, West German Cancer Centre, University of Duisburg-Essen, Hufelandstra├če, Essen, Germany., Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Early Clinical Trial Unit, University Cancer Center, Dresden, Germany., Pfizer, Inc, New York, NY, USA., Merck KGaA, Darmstadt, Germany., EMD Serono Inc, Rockland, MA, USA., EMD Serono Research and Development Institute, Billerica, MA, USA., National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.