Real-world efficacy of cabozantinib alone or in combination with ICIs in heavily pretreated hepatocellular carcinoma: potential role of AXL and MET expression
Introduction and Objectives: Cabozantinib, a multi-kinase inhibitor targeting AXL and MET, is approved for second-line treatment of hepatocellular carcinoma (HCC). However, the combination of cabozantinib with immune checkpoint inhibitors (ICIs) remains controversial after the COSMIC-312 study. The...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
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| Series: | Annals of Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268125001425 |
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| Summary: | Introduction and Objectives: Cabozantinib, a multi-kinase inhibitor targeting AXL and MET, is approved for second-line treatment of hepatocellular carcinoma (HCC). However, the combination of cabozantinib with immune checkpoint inhibitors (ICIs) remains controversial after the COSMIC-312 study. The role of AXL and MET expression in predicting cabozantinib response is unclear. This study aims to evaluate cabozantinib's efficacy with ICIs and the predictive value of AXL and MET expression. Materials and Methods: From January 2019 and December 2023, 50 advanced HCC patients treated with cabozantinib were retrospectively enrolled. Results: Overall, 74% of patients received prior immunotherapy, 72% had been treated with more than two different multiple kinase inhibitors (MKIs), and 58% received cabozantinib as a fifth-line or later therapy. Cabozantinib was used alone (60%), with ICIs (12%), or with chemotherapy (28%). A majority (70%) received a dosage exceeding 40 mg/day. The ORR to cabozantinib was 0%, while the DCR was 42.2%. median PFS was 3.3 months, and OS was 6.1 months. There was no significant difference in PFS or OS between patients receiving five or more lines of treatment and those receiving fewer. Cabozantinib plus ICIs showed longer PFS (6.7 vs. 3.2 months, p = 0.04) and a trend toward improved OS compared to cabozantinib alone. AXL expression may predict better outcomes. Common adverse effects included palmar-plantar erythrodysesthesia (24.2%) and hypertension. Conclusions: This study highlights the potential of cabozantinib combined with immunotherapy in heavily pretreated HCC, with AXL expression as a possible predictive biomarker. |
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| ISSN: | 1665-2681 |