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

Autor: Joanne Chiu, Thomas Yau, Chung Mau Lo, Bryan Cho Wing Li, Jeffrey Sum Lung Wong, Ka Wing Ma, Josephine Tsang, Gerry Gin Wai Kwok, Tan To Cheung, Vikki Tang, Roland Leung, Wong Hoi She
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
Time Factors
medicine.medical_treatment
Pembrolizumab
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Tumor Microenvironment
Immunology and Allergy
Immune Checkpoint Inhibitors
RC254-282
Aged
80 and over
Clinical/Translational Cancer Immunotherapy
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Middle Aged
drug therapy
Nivolumab
Treatment Outcome
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Disease Progression
Molecular Medicine
Female
immunotherapy
medicine.drug
CTLA-4 antigen
medicine.medical_specialty
Carcinoma
Hepatocellular
Immunology
Ipilimumab
Antibodies
Monoclonal
Humanized
programmed cell death 1 receptor
03 medical and health sciences
Refractory
Internal medicine
medicine
Humans
Adverse effect
Aged
Retrospective Studies
Salvage Therapy
combination
Pharmacology
liver neoplasms
business.industry
Immunotherapy
medicine.disease
030104 developmental biology
Drug Resistance
Neoplasm
Tumor progression
business
Zdroj: Journal for Immunotherapy of Cancer
Journal for ImmunoTherapy of Cancer, Vol 9, Iss 2 (2021)
ISSN: 2051-1426
Popis: 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 pConclusionsIpilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.
Databáze: OpenAIRE
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