Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040
Background: Patients with advanced hepatocellular carcinoma (aHCC) have a poor prognosis and high mortality. Nivolumab monotherapy demonstrated clinical benefit with an acceptable safety profile in patients with aHCC in the CheckMate 040 study. Five-year follow-up of the sorafenib-naive and sorafeni...
| Autores: | , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/68695 |
| Acceso en línea: | https://hdl.handle.net/10171/68695 |
| Access Level: | acceso abierto |
| Palabra clave: | Advanced hepatocellular carcinoma Checkpoint inhibitor Nivolumab Sorafenib |
| id |
ES_8e1255c19a97c5772baeecd18435308b |
|---|---|
| oai_identifier_str |
oai:dadun.unav.edu:10171/68695 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| spelling |
Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040El-Khoueiry, A. (Anthony)|||/items/8144acbd-0107-4f48-8776-9e28947910d4Trojan, J. (Jörg)|||/items/24929b81-6829-4a40-b886-bd4356930b88Meyer, T. (Tim)|||/items/8c2802cc-2ef6-47ba-ac7e-8e5c645b6dcdYau, T. (Thomas)|||/items/4f76bdb4-81e1-4c13-9b6d-5fb062c44c0cMelero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4eKudo, M. (Masatoshi)|||/items/ca6675fa-6f9a-4b9b-a1d1-940a9b2cdcb4Hsu, C. (Chiun)|||/items/dada2477-6351-4094-96b2-269cb671a39eKim, T.Y. (Tae-You)|||/items/2aa11a88-db46-4b2b-a9d2-40e9f92ee653Choo, S.P. (Su-Pin)|||/items/7436d628-e6c7-42f3-ae60-d9f1aa8795f7Kang, Y.K. (Yoon-Koo)|||/items/a0ac8423-47c6-4698-810f-fd3284864332Yeo, W. (W.)|||/items/a43d2c64-b244-44c6-9a56-514de192c832Chopra, A. (A.)|||/items/bc4739a1-2bf7-4741-ba21-65e4fe11069cSoleymani, S. (S.)|||/items/a6773278-312f-4b55-b855-7bdaf9b34030Yao, J. (J.)|||/items/bd04f3e2-80cb-403d-b657-46d9e0960ce7Neely, J. (Jaclyn)|||/items/9b534b77-1e41-471f-adc0-8658a0a64392Tschaika, M. (Marina)|||/items/c5f80258-6e8c-4d51-89fc-4c1ec414ef3aWelling, T.H. (T. H.)|||/items/d169ce19-db70-4a0c-ba92-043fee4b523fSangro-Gómez-Acebo, B.C. (Bruno Carlos)|||/items/594bbdbb-046a-4ab2-878c-cb4fe577af49Advanced hepatocellular carcinomaCheckpoint inhibitorNivolumabSorafenibBackground: Patients with advanced hepatocellular carcinoma (aHCC) have a poor prognosis and high mortality. Nivolumab monotherapy demonstrated clinical benefit with an acceptable safety profile in patients with aHCC in the CheckMate 040 study. Five-year follow-up of the sorafenib-naive and sorafenib-experienced cohorts of CheckMate 040 are presented here. Patients and methods: Patients received nivolumab monotherapy at dose levels of 0.1-10.0 mg/kg (dose-escalation phase) or 3 mg/kg (dose-expansion phase) every 2 weeks until disease progression or unacceptable toxicity. Primary endpoints were safety and tolerability (dose escalation), and objective response rate (ORR) by blinded independent central review (BICR) and by investigator per RECIST version 1.1 (dose expansion). Results: Eighty sorafenib-naive and 154 sorafenib-experienced patients were treated. Minimum follow-up in both groups was 60 months. ORR per BICR was 20% (95% CI 12-30) and 14% (95% CI 9-21) in the sorafenib-naive and sorafenib-experienced groups, respectively. Responses occurred regardless of HCC etiology or baseline tumor cell programmed death ligand 1 (PD-L1) expression levels. Median overall survival (OS) was 26.6 months (95% CI 16.6-30.6) and 15.1 months (95% CI 13.0-18.2) in sorafenib-naive and sorafenib-experienced patients, respectively. The 3-year OS rates were 28% in the sorafenib-naive and 20% in the sorafenib-experienced group; 5-year OS rates were 14% and 12%, respectively. No new safety signals were identified; grade 3/4 treatment-related adverse events were observed in 33% and 21% in the sorafenib-naive and sorafenib-experienced patients, respectively. Biomarker analyses showed that baseline PD-L1 expression ≥1% was associated with higher ORR and longer OS compared with PD-L1 <1%. In the sorafenib-naive group, patients with OS ≥3 years exhibited higher baseline CD8 T-cell density compared with those with OS <1 year. Conclusion: With 5 years of follow-up, nivolumab monotherapy continued to provide durable clinical benefit with manageable safety in sorafenib-naive and sorafenib-experienced patients with aHCC.ElsevierDadun. Depósito Académico Digital Universidad de Navarra20242024-02-0120232023-01-0120232023-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/68695reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/686952026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040 |
| title |
Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040 |
| spellingShingle |
Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040 El-Khoueiry, A. (Anthony)|||/items/8144acbd-0107-4f48-8776-9e28947910d4 Advanced hepatocellular carcinoma Checkpoint inhibitor Nivolumab Sorafenib |
| title_short |
Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040 |
| title_full |
Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040 |
| title_fullStr |
Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040 |
| title_full_unstemmed |
Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040 |
| title_sort |
Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040 |
| dc.creator.none.fl_str_mv |
El-Khoueiry, A. (Anthony)|||/items/8144acbd-0107-4f48-8776-9e28947910d4 Trojan, J. (Jörg)|||/items/24929b81-6829-4a40-b886-bd4356930b88 Meyer, T. (Tim)|||/items/8c2802cc-2ef6-47ba-ac7e-8e5c645b6dcd Yau, T. (Thomas)|||/items/4f76bdb4-81e1-4c13-9b6d-5fb062c44c0c Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e Kudo, M. (Masatoshi)|||/items/ca6675fa-6f9a-4b9b-a1d1-940a9b2cdcb4 Hsu, C. (Chiun)|||/items/dada2477-6351-4094-96b2-269cb671a39e Kim, T.Y. (Tae-You)|||/items/2aa11a88-db46-4b2b-a9d2-40e9f92ee653 Choo, S.P. (Su-Pin)|||/items/7436d628-e6c7-42f3-ae60-d9f1aa8795f7 Kang, Y.K. (Yoon-Koo)|||/items/a0ac8423-47c6-4698-810f-fd3284864332 Yeo, W. (W.)|||/items/a43d2c64-b244-44c6-9a56-514de192c832 Chopra, A. (A.)|||/items/bc4739a1-2bf7-4741-ba21-65e4fe11069c Soleymani, S. (S.)|||/items/a6773278-312f-4b55-b855-7bdaf9b34030 Yao, J. (J.)|||/items/bd04f3e2-80cb-403d-b657-46d9e0960ce7 Neely, J. (Jaclyn)|||/items/9b534b77-1e41-471f-adc0-8658a0a64392 Tschaika, M. (Marina)|||/items/c5f80258-6e8c-4d51-89fc-4c1ec414ef3a Welling, T.H. (T. H.)|||/items/d169ce19-db70-4a0c-ba92-043fee4b523f Sangro-Gómez-Acebo, B.C. (Bruno Carlos)|||/items/594bbdbb-046a-4ab2-878c-cb4fe577af49 |
| author |
El-Khoueiry, A. (Anthony)|||/items/8144acbd-0107-4f48-8776-9e28947910d4 |
| author_facet |
El-Khoueiry, A. (Anthony)|||/items/8144acbd-0107-4f48-8776-9e28947910d4 Trojan, J. (Jörg)|||/items/24929b81-6829-4a40-b886-bd4356930b88 Meyer, T. (Tim)|||/items/8c2802cc-2ef6-47ba-ac7e-8e5c645b6dcd Yau, T. (Thomas)|||/items/4f76bdb4-81e1-4c13-9b6d-5fb062c44c0c Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e Kudo, M. (Masatoshi)|||/items/ca6675fa-6f9a-4b9b-a1d1-940a9b2cdcb4 Hsu, C. (Chiun)|||/items/dada2477-6351-4094-96b2-269cb671a39e Kim, T.Y. (Tae-You)|||/items/2aa11a88-db46-4b2b-a9d2-40e9f92ee653 Choo, S.P. (Su-Pin)|||/items/7436d628-e6c7-42f3-ae60-d9f1aa8795f7 Kang, Y.K. (Yoon-Koo)|||/items/a0ac8423-47c6-4698-810f-fd3284864332 Yeo, W. (W.)|||/items/a43d2c64-b244-44c6-9a56-514de192c832 Chopra, A. (A.)|||/items/bc4739a1-2bf7-4741-ba21-65e4fe11069c Soleymani, S. (S.)|||/items/a6773278-312f-4b55-b855-7bdaf9b34030 Yao, J. (J.)|||/items/bd04f3e2-80cb-403d-b657-46d9e0960ce7 Neely, J. (Jaclyn)|||/items/9b534b77-1e41-471f-adc0-8658a0a64392 Tschaika, M. (Marina)|||/items/c5f80258-6e8c-4d51-89fc-4c1ec414ef3a Welling, T.H. (T. H.)|||/items/d169ce19-db70-4a0c-ba92-043fee4b523f Sangro-Gómez-Acebo, B.C. (Bruno Carlos)|||/items/594bbdbb-046a-4ab2-878c-cb4fe577af49 |
| author_role |
author |
| author2 |
Trojan, J. (Jörg)|||/items/24929b81-6829-4a40-b886-bd4356930b88 Meyer, T. (Tim)|||/items/8c2802cc-2ef6-47ba-ac7e-8e5c645b6dcd Yau, T. (Thomas)|||/items/4f76bdb4-81e1-4c13-9b6d-5fb062c44c0c Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e Kudo, M. (Masatoshi)|||/items/ca6675fa-6f9a-4b9b-a1d1-940a9b2cdcb4 Hsu, C. (Chiun)|||/items/dada2477-6351-4094-96b2-269cb671a39e Kim, T.Y. (Tae-You)|||/items/2aa11a88-db46-4b2b-a9d2-40e9f92ee653 Choo, S.P. (Su-Pin)|||/items/7436d628-e6c7-42f3-ae60-d9f1aa8795f7 Kang, Y.K. (Yoon-Koo)|||/items/a0ac8423-47c6-4698-810f-fd3284864332 Yeo, W. (W.)|||/items/a43d2c64-b244-44c6-9a56-514de192c832 Chopra, A. (A.)|||/items/bc4739a1-2bf7-4741-ba21-65e4fe11069c Soleymani, S. (S.)|||/items/a6773278-312f-4b55-b855-7bdaf9b34030 Yao, J. (J.)|||/items/bd04f3e2-80cb-403d-b657-46d9e0960ce7 Neely, J. (Jaclyn)|||/items/9b534b77-1e41-471f-adc0-8658a0a64392 Tschaika, M. (Marina)|||/items/c5f80258-6e8c-4d51-89fc-4c1ec414ef3a Welling, T.H. (T. H.)|||/items/d169ce19-db70-4a0c-ba92-043fee4b523f Sangro-Gómez-Acebo, B.C. (Bruno Carlos)|||/items/594bbdbb-046a-4ab2-878c-cb4fe577af49 |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Advanced hepatocellular carcinoma Checkpoint inhibitor Nivolumab Sorafenib |
| topic |
Advanced hepatocellular carcinoma Checkpoint inhibitor Nivolumab Sorafenib |
| description |
Background: Patients with advanced hepatocellular carcinoma (aHCC) have a poor prognosis and high mortality. Nivolumab monotherapy demonstrated clinical benefit with an acceptable safety profile in patients with aHCC in the CheckMate 040 study. Five-year follow-up of the sorafenib-naive and sorafenib-experienced cohorts of CheckMate 040 are presented here. Patients and methods: Patients received nivolumab monotherapy at dose levels of 0.1-10.0 mg/kg (dose-escalation phase) or 3 mg/kg (dose-expansion phase) every 2 weeks until disease progression or unacceptable toxicity. Primary endpoints were safety and tolerability (dose escalation), and objective response rate (ORR) by blinded independent central review (BICR) and by investigator per RECIST version 1.1 (dose expansion). Results: Eighty sorafenib-naive and 154 sorafenib-experienced patients were treated. Minimum follow-up in both groups was 60 months. ORR per BICR was 20% (95% CI 12-30) and 14% (95% CI 9-21) in the sorafenib-naive and sorafenib-experienced groups, respectively. Responses occurred regardless of HCC etiology or baseline tumor cell programmed death ligand 1 (PD-L1) expression levels. Median overall survival (OS) was 26.6 months (95% CI 16.6-30.6) and 15.1 months (95% CI 13.0-18.2) in sorafenib-naive and sorafenib-experienced patients, respectively. The 3-year OS rates were 28% in the sorafenib-naive and 20% in the sorafenib-experienced group; 5-year OS rates were 14% and 12%, respectively. No new safety signals were identified; grade 3/4 treatment-related adverse events were observed in 33% and 21% in the sorafenib-naive and sorafenib-experienced patients, respectively. Biomarker analyses showed that baseline PD-L1 expression ≥1% was associated with higher ORR and longer OS compared with PD-L1 <1%. In the sorafenib-naive group, patients with OS ≥3 years exhibited higher baseline CD8 T-cell density compared with those with OS <1 year. Conclusion: With 5 years of follow-up, nivolumab monotherapy continued to provide durable clinical benefit with manageable safety in sorafenib-naive and sorafenib-experienced patients with aHCC. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023 2023-01-01 2023 2023-01-01 2024 2024-02-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/68695 |
| url |
https://hdl.handle.net/10171/68695 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| dc.source.none.fl_str_mv |
reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
| instname_str |
Universidad de Navarra |
| reponame_str |
Dadun. Depósito Académico Digital de la Universidad de Navarra |
| collection |
Dadun. Depósito Académico Digital de la Universidad de Navarra |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869413098621763584 |
| score |
15,300724 |