Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

• Published in: Journal for immunotherapy of cancer 2021-02, Vol.9 (2), p.e001945
• Main Authors: Wong, Jeffrey Sum Lung, Kwok, Gerry Gin Wai, Tang, Vikki, Li, Bryan Cho Wing, Leung, Roland, Chiu, Joanne, Ma, Ka Wing, She, Wong Hoi, Tsang, Josephine, Lo, Chung Mau, Cheung, Tan To, Yau, Thomas
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antibodies; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Cancer; Cancer therapies; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Cell death; Clinical/Translational Cancer Immunotherapy; Disease Progression; Drug Resistance, Neoplasm; FDA approval; Female; Hepatitis; Humans; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Investigations; Ipilimumab - adverse effects; Ipilimumab - therapeutic use; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - immunology; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Male; Middle Aged; Monoclonal antibodies; Nivolumab - adverse effects; Nivolumab - therapeutic use; Proteins; Regulatory approval; Retrospective Studies; Salvage Therapy; Targeted cancer therapy; Time Factors; Treatment Outcome; Tumor Microenvironment; Tumors
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2020-001945

BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p