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

TitleIpilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors
Authors
Issue Date2021
PublisherBMJ Publishing Group: Open Access Journals. The Journal's web site is located at http://www.immunotherapyofcancer.org/
Citation
Journal for ImmunoTherapy of Cancer, 2021, v. 9 n. 2, p. article no. e001945 How to Cite?
AbstractBackground: Programmed 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. Methods: Patients 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. Results: Twenty-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<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs. Conclusions: Ipilimumab 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.
Persistent Identifierhttp://hdl.handle.net/10722/305385
ISSN
2023 Impact Factor: 10.3
2023 SCImago Journal Rankings: 3.728
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, JSL-
dc.contributor.authorKwok, GGW-
dc.contributor.authorTang, V-
dc.contributor.authorLi, BCW-
dc.contributor.authorLeung, R-
dc.contributor.authorChiu, J-
dc.contributor.authorMa, KW-
dc.contributor.authorShe, WH-
dc.contributor.authorTsang, J-
dc.contributor.authorLo, CM-
dc.contributor.authorCheung, TT-
dc.contributor.authorYau, T-
dc.date.accessioned2021-10-20T10:08:39Z-
dc.date.available2021-10-20T10:08:39Z-
dc.date.issued2021-
dc.identifier.citationJournal for ImmunoTherapy of Cancer, 2021, v. 9 n. 2, p. article no. e001945-
dc.identifier.issn2051-1426-
dc.identifier.urihttp://hdl.handle.net/10722/305385-
dc.description.abstractBackground: Programmed 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. Methods: Patients 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. Results: Twenty-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<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs. Conclusions: Ipilimumab 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.-
dc.languageeng-
dc.publisherBMJ Publishing Group: Open Access Journals. The Journal's web site is located at http://www.immunotherapyofcancer.org/-
dc.relation.ispartofJournal for ImmunoTherapy of Cancer-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleIpilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors-
dc.typeArticle-
dc.identifier.emailTang, V: vyftang@hku.hk-
dc.identifier.emailLi, BCW: bryanli@hku.hk-
dc.identifier.emailChiu, J: jwychiu@hku.hk-
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hk-
dc.identifier.emailCheung, TT: cheung68@hku.hk-
dc.identifier.emailYau, T: tyaucc@hku.hk-
dc.identifier.authorityChiu, J=rp01917-
dc.identifier.authorityMa, KW=rp02758-
dc.identifier.authorityLo, CM=rp00412-
dc.identifier.authorityCheung, TT=rp02129-
dc.identifier.authorityYau, T=rp01466-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1136/jitc-2020-001945-
dc.identifier.scopuseid_2-s2.0-85100968399-
dc.identifier.hkuros326655-
dc.identifier.volume9-
dc.identifier.issue2-
dc.identifier.spagearticle no. e001945-
dc.identifier.epagearticle no. e001945-
dc.identifier.isiWOS:000617737700001-
dc.publisher.placeUnited Kingdom-

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