Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040

A B El-Khoueiry; J Trojan; T Meyer; T Yau; I Melero; M Kudo; C Hsu; T-Y Kim; S-P Choo; Y-K Kang; W Yeo; A Chopra; S Soleymani; J Yao; J Neely; M Tschaika; T H Welling; B Sangro

doi:10.1016/j.annonc.2023.12.008

Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040

Ann Oncol. 2024 Apr;35(4):381-391. doi: 10.1016/j.annonc.2023.12.008. Epub 2023 Dec 25.

Authors

A B El-Khoueiry¹, J Trojan², T Meyer³, T Yau⁴, I Melero⁵, M Kudo⁶, C Hsu⁷, T-Y Kim⁸, S-P Choo⁹, Y-K Kang¹⁰, W Yeo¹¹, A Chopra¹², S Soleymani¹³, J Yao¹⁴, J Neely¹⁵, M Tschaika¹⁶, T H Welling¹⁷, B Sangro¹⁸

Affiliations

¹ Division of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, USA. Electronic address: elkhouei@usc.edu.
² Department of Medicine, Goethe University Hospital and Cancer Center, Frankfurt, Germany.
³ Department of Oncology, Royal Free Hospital, London, UK.
⁴ Department of Medicine, University of Hong Kong, Hong Kong, China.
⁵ Department of Immunology, Clinica Universidad de Navarra and CIBERONC, Pamplona, Spain.
⁶ Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
⁷ Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
⁸ Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
⁹ Division of Medical Oncology, National Cancer Center and Curie Oncology, Singapore, Republic of Singapore.
¹⁰ Department of Oncology, Asan Medical Center, University of Ulsan, Seoul, Korea.
¹¹ Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China.
¹² Department of Medical Oncology, Johns Hopkins Singapore International Medical Centre, Singapore, Republic of Singapore.
¹³ Global Biometrics & Data Sciences, Bristol Myers Squibb, Princeton, USA.
¹⁴ Informatics and Predictive Sciences, Bristol Myers Squibb, Princeton, USA.
¹⁵ Translational Medicine, Bristol Myers Squibb, Princeton, USA.
¹⁶ Oncology Clinical Development, Bristol Myers Squibb, Princeton, USA.
¹⁷ Perlmutter Cancer Center and Department of Surgery, NYU Langone Health, New York, USA.
¹⁸ Liver Unit and HPB Oncology Area, Clinica Universidad de Navarra and CIBEREHD, Pamplona, Spain.

PMID: 38151184
DOI: 10.1016/j.annonc.2023.12.008

Abstract

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 groups of CheckMate 040 is 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 as 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 as per BICR was 20% [95% confidence interval (CI) 12% to 30%] and 14% (95% CI 9% to 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 months) and 15.1 months (95% CI 13.0-18.2 months) 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 groups; 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% of patients in the sorafenib-naive and sorafenib-experienced groups, 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.

Keywords: advanced hepatocellular carcinoma; checkpoint inhibitor; nivolumab; sorafenib.

Publication types

Clinical Trial, Phase I

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / therapeutic use
B7-H1 Antigen / metabolism
Carcinoma, Hepatocellular* / drug therapy
Follow-Up Studies
Humans
Ipilimumab / therapeutic use
Liver Neoplasms* / drug therapy
Nivolumab / adverse effects
Sorafenib / therapeutic use

Substances

Nivolumab
Sorafenib
B7-H1 Antigen
Ipilimumab