Neratinib Alone or in Combination with Immune Checkpoint Inhibitors with or without Mammalian Target of Rapamycin Inhibitors in Patients with Fibrolamellar Carcinoma.
Document Type
Article
Publication Date
2025
Publication Title
Liver Cancer
Abstract
INTRODUCTION: Fibrolamellar carcinoma (FLC) displays upregulation of several oncogenes, including
METHODS: Patients received neratinib 240 mg/day orally in SUMMIT, or as doublet or triplet combinations with pembrolizumab 2 mg/kg intravenously every 3 weeks, nivolumab 240 mg intravenously every 2 weeks, everolimus 7.5 mg/day orally, or sunitinib 37.5 mg/day orally under compassionate use. The primary endpoint in SUMMIT was objective response rate; safety was a secondary endpoint.
RESULTS: Fifteen patients with FLC received neratinib monotherapy in SUMMIT. The objective response rate was 5% (95% confidence interval [CI]: 0-21.8) and the disease control rate was 13.3% (95% CI: 1.7-40.5). Upon progression, five had added immune checkpoint inhibitors with or without everolimus or sunitinib. Two additional patients received neratinib-based combinations outside of SUMMIT, for a total of 17 neratinib-treated patients. One patient who received neratinib plus pembrolizumab had a confirmed partial response, one treated with neratinib plus everolimus had stable disease lasting 6 months, and one who received neratinib plus pembrolizumab plus sunitinib had stable disease lasting 16 months. Grade 3/4 adverse events with neratinib monotherapy occurred in 10 (66.7%)/2 (13.3%) patients, respectively. Grade 3 adverse events with neratinib-based combinations were hyperglycemia (n = 1; neratinib plus pembrolizumab), hepatic failure, and anaphylaxis (n = 1 each, neratinib plus pembrolizumab plus everolimus). There were no grade 4 adverse events with combination therapy.
CONCLUSION: In patients with FLC, single-agent neratinib had limited efficacy, but clinical benefit was observed with neratinib in combination with immunotherapy and/or mTOR-targeted agents.
Volume
14
Issue
1
First Page
58
Last Page
67
Recommended Citation
Abou-Alfa GK, Meyer T, Do RKG, Piha-Paul SA, Light JS, Sherrin S, et al [Cornelius AS]. Neratinib alone or in combination with immune checkpoint inhibitors with or without mammalian target of rapamycin inhibitors in patients with fibrolamellar carcinoma. Liver Cancer. 2025;14(1):58-67. doi: 10.1159/000540290. PMID: 40144471.
DOI
10.1159/000540290
ISSN
2235-1795
PubMed ID
40144471
Comments
Helen DeVos Children's Hospital