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Title: Evaluation of Combination Nivolumab and Ipilimumab Immunotherapy in Patients With Advanced Biliary Tract Cancers: Subgroup Analysis of a Phase 2 Nonrandomized Clinical Trial.
Austin Authors: Klein, Oliver ;Kee, Damien ;Nagrial, Adnan;Markman, Ben;Underhill, Craig;Michael, Michael;Jackett, Louise A ;Lum, Caroline;Behren, Andreas;Palmer, Jodie ;Tebbutt, Niall C ;Carlino, Matteo S;Cebon, Jonathan S 
Affiliation: Albury-Wodonga Regional Cancer Centre, Albury-Wodonga, Australia
Monash University, Melbourne, Australia
Blacktown Hospital and the University of Sydney, Sydney, Australia
Department of Medical Oncology, Austin Health, Heidelberg, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Australia
Department of Medical Oncology, Monash Health, Melbourne, Australia
Department of Surgery, University of Melbourne, Melbourne, Australia
Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
Issue Date: 1-Sep-2020 2020-07-30
Publication information: JAMA Oncology 2020; 6(9): 1405-1409
Abstract: Biliary tract cancers represent a rare group of malignant conditions with very limited treatment options. Patients with advanced disease have a poor outcome with current therapies. To evaluate the efficacy and safety of combination immunotherapy with nivolumab and ipilimumab in patients with advanced biliary tract cancers. The CA209-538 prospective multicenter phase 2 nonrandomized clinical trial included patients with advanced rare cancers including patients with biliary tract cancers. This subgroup analysis evaluated 39 patients from CA209-538 with biliary tract cancers who were enrolled from December 2017 to December 2019. Most of the patients (n = 33) had experienced disease progression after 1 or more lines of therapy and had tumor tissue available for biomarker research. Patients received treatment with nivolumab at a dose of 3 mg/kg and ipilimumab at 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg every 2 weeks and continued for up to 96 weeks until disease progression or the development of unacceptable toxic events. The primary end point was disease control rate (complete remission, partial remission, or stable disease) as assessed by RECIST 1.1. Among the 39 patients included in this subgroup analysis of a phase 2 clinical trial (20 men, 19 women; mean [range] age, 65 [37-81] years), the objective response rate was 23% (n = 9) with a disease control rate of 44% (n = 17); all responders had received prior chemotherapy, and none had a microsatellite unstable tumor. Responses were exclusively observed in patients with intrahepatic cholangiocarcinoma and gallbladder carcinoma. The median duration of response was not reached (range, 2.5 to ≥23 months). The median progression-free survival was 2.9 months (95% CI, 2.2-4.6 months), and overall survival was 5.7 months (95% CI, 2.7-11.9 months). Immune-related toxic events were reported in 49% of patients (n = 19), with 15% (n = 6) experiencing grade 3 or 4 events. This subgroup analysis of a phase 2 clinical trial found that combination immunotherapy with nivolumab and ipilimumab was associated with substantial positive outcomes patients with advanced biliary tract cancers. This treatment compares favorably to single-agent anti-programmed cell death protein 1 (anti-PD-1) therapy and warrants further investigation. Ongoing translational research is focused on identifying biomarkers that can predict treatment response. Identifier: NCT02923934.
DOI: 10.1001/jamaoncol.2020.2814
ORCID: 0000-0002-3898-950X
Journal: JAMA oncology
PubMed URL: 32729929
Type: Journal Article
Appears in Collections:Journal articles

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