Hepatic safety and biomarker assessments in sorafenib-experienced patients with advanced hepatocellular carcinoma treated with nivolumab in the CheckMate-040 study
Refereed conference paper presented and published in conference proceedings


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AbstractBackground and Aims: The majority of patients (pts) with advanced HCC (aHCC) progress on sorafenib (sor) therapy. Nivolumab (NIVO) is a fully human anti–PD-1 IgG4 mAb that demonstrated durable responses, manageable safety, and long-term survival in pts with aHCC in CheckMate-040 (El-Khoueiry AB, Sangro B, et al. Lancet 2017). Here we present updated hepatic safety and biomarker analyses in sor-experienced (sor-exp) pts with aHCC in CheckMate- 040.

Method: Sor-exp pts with or without chronic viral hepatitis received NIVO 3 mg/kg Q2W in the dose-expansion phase (EXP) regardless of PD-L1 status. Primary endpoint was objective response rate (ORR) reported by blinded independent central review using RECIST v1.1 (EXP). Secondary endpoints included overall survival (OS), disease control rate (DCR), and safety. Exploratory analyses of on-treatment HCV and HBV viral kinetics and alpha-fetoprotein (AFP) levels were performed.

Results: Median duration of follow-up was 14.9 mo in sor-exp pts (N = 145), 132 (91%) of whom had progressed on sor. Baseline Child- Pugh scores of 5 or 6 and extrahepatic metastases were observed in 99% and 71% of pts, respectively. The ORR with NIVO was 14%; the DCR was 56%; median OS was 15.6 mo. Any-grade and grade 3–4 hepatic treatment-related AEs (TRAEs) occurred in 12 (8%) and 5 (3%) pts, respectively; 100% of grade 3–4 hepatic TRAEs resolved. Frequencies of grade 3–4 treatment-related ALT/AST elevations were 2–3%. No drug-related deaths due to hepatic AEs occurred, and no new safety signals were observed. Among HBV-infected pts, 8% (3 of 38) had a >1 log decrease in HBsAg, and 12% (5 of 41) had a >1 log increase in HBV DNA. HBV DNA increases did not result in changes in hepatic parameters or serious AEs. Among HCV-infected pts, 30% (8 of 27) had a >1 log decrease in HCV RNA. Median baseline AFP in responders (165 μg/L) and nonresponders (85 μg/L) was similar (p = 0.5898). For pts with baseline AFP ≥10 μg/L, on treatment AFP declines >1 log occurred in 94% of responders and10% of nonresponders. Updated data will be presented.

Conclusion: NIVO demonstrated long-term survival and objective responses across etiologies in sor-exp pts with aHCC. The manageable safety profile of NIVO, including immune-mediated and hepatic AEs,was consistent with other tumor types in which NIVO is approved. NIVO had limited impact on viral kinetics in HBV and HCV-infected pts. Responses occurred irrespective of baseline AFP levels, and AFP declines were associated with response.
All Author(s) ListTim Meyer, Ignacio Melero, Thomas Yau, Chiun Hsu, Masatoshi Kudo, Su-Pin Choo, Jörg Trojan, Theodore H. Welling, Yoon-Koo Kang, Winnie Yeo, Akhil Chopra, Adyb Baakili, Christine dela Cruz, Huanyu Zhao, Jaclyn Neely, odd S. Crocenzi, Anthony B. El-Khoueiry, Bruno Sangro
Name of ConferenceThe International Liver Congress 2018 EASL - European Association for the Study of the Liver
Start Date of Conference11/04/2018
End Date of Conference15/04/2018
Place of ConferenceParis
Country/Region of ConferenceFrance
Proceedings TitleJournal of Hepatology
Year2018
Month4
Volume Number68
Issue NumberSuppl 1
PublisherElsevier
PagesS16 - S16
LanguagesEnglish-United Kingdom
Keywordshepatocellular carcinoma, nivolumab

Last updated on 2020-10-08 at 03:32