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. 2025 Sep 1;30(9):oyaf252.
doi: 10.1093/oncolo/oyaf252.

Real-world clinical outcomes of cabozantinib as a second-line treatment for advanced hepatocellular carcinoma: a retrospective US claims analysis

Daniel H Ahn  1 , Noh Jin Park  2 , Michael Locker  2 , Zheng-Yi Zhou  3 , Xiaoyu Nie  3 , Travis Wang  3 , Shengsheng Yu  2
Affiliations

Real-world clinical outcomes of cabozantinib as a second-line treatment for advanced hepatocellular carcinoma: a retrospective US claims analysis

Daniel H Ahn et al. Oncologist. .

Abstract

Background: Cabozantinib is indicated for hepatocellular carcinoma (HCC) following first-line (1L) sorafenib, but the 1L standard has shifted to immuno-oncology (IO)-based regimens. This study evaluated real-world outcomes among patients with advanced HCC receiving second-line (2L) cabozantinib following 1L therapies, including newer regimens.

Patients and methods: US claims data were used to identify adults with advanced HCC initiating 2L cabozantinib monotherapy (index date). Patients were stratified into three 1L treatment cohorts: IO monotherapy/IO + IO combination therapy; IO + non-IO combination therapy; or tyrosine kinase inhibitor (TKI) monotherapy. Real-world time to treatment discontinuation (rwTTD), real-world time to next treatment or death (rwTNTD), real-world overall survival (rwOS), and cabozantinib dosing were assessed collectively and by cohort. Adverse events were assessed before/after cabozantinib initiation.

Results: Among 148 patients who received 2L cabozantinib, 28 were in the IO monotherapy/IO + IO combination therapy cohort, 54 in the IO + non-IO combination therapy cohort, and 66 in the TKI monotherapy cohort. Median rwTTD among all patients was 3.2 months; median rwTNTD was 7.6 months; 12-month rwOS rate was 61.6%. There were no significant differences in these outcomes among the three cohorts. Overall, 44.6% of patients initiated 2L cabozantinib at 60 mg/day, of whom 39.4% required a dose reduction; 37.8% initiated at 40 mg/day, of whom 16.1% had a dose reduction. Adverse event rates were similar before/after cabozantinib initiation.

Conclusions: Cabozantinib shows consistent effectiveness and safety in the 2L HCC setting following prior TKIs or IO-based regimens in real-world clinical practice. These findings may inform 2L treatment decisions.

Keywords: cabozantinib; hepatocellular carcinoma; retrospective studies; treatment outcome.

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Conflict of interest statement

D.H.A. reports research funding from Bayer and AstraZeneca; receipt of travel accommodations/expenses from Genentech, Incyte, and Exelixis; participation on a data safety monitoring board or advisory board for Exelixis, Genentech, Advanced Accelerator Applications, and Incyte; and stock or stock options in Natera. N.J.P., M.L., and S.Y. are employees of Exelixis, Inc., the manufacturer of cabozantinib. Z.-Y.Z., X.N., and T.W. are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Exelixis, Inc., which funded the development and conduct of this study and manuscript. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Figures

Figure 1.
Figure 1.
Sample selection. aNCCN-recommended systemic therapies include atezolizumab + bevacizumab, sorafenib, lenvatinib, durvalumab, pembrolizumab, nivolumab, regorafenib, cabozantinib, ramucirumab, nivolumab + ipilimumab, dostarlimab-gxly, and selpercatinib. Some of these regimens are only recommended as subsequent-line systemic therapy options in the NCCN guidelines. However, whether a regimen was received in a line of therapy consistent with NCCN recommendations was not a selection criterion of our study sample. No patient in the data received tremelimumab, since the study period barely overlaps with the approval date of durvalumab + tremelimumab by the Food and Drug Administration (i.e., October 21, 2022). bOne patient who received ramucirumab monotherapy in 1L was excluded from the final sample. Abbreviations: 1/2L, first/second line; combo, combination therapy; HCC, hepatocellular carcinoma; ICD-10-CM, International Classification of Diseases, Tenth Revision, Clinical Modification; IO, immuno-oncology; mono, monotherapy; NCCN, National Comprehensive Cancer Network; TKI, tyrosine kinase inhibitor.
Figure 2.
Figure 2.
rwTTD of 2L cabozantinib stratified by 1L therapy. Abbreviations: 1/2L, first/second line; CI, confidence interval; combo, combination therapy; IO, immuno-oncology; mono, monotherapy; rwTTD, real-world time to treatment discontinuation; TKI, tyrosine kinase inhibitor.
Figure 3.
Figure 3.
rwTNTD of 2L cabozantinib stratified by 1L therapy. Abbreviations: 1/2L, first/second line; CI, confidence interval; combo, combination therapy; IO, immuno-oncology; mono, monotherapy; rwTNTD, real-world time to next treatment or death; TKI, tyrosine kinase inhibitor.
Figure 4.
Figure 4.
rwOS of 2L cabozantinib stratified by 1L therapy. Abbreviations: 1/2L, first/second line; combo, combination therapy; IO, immuno-oncology; mono, monotherapy; rwOS, real-world overall survival; TKI, tyrosine kinase inhibitor.
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