1000P - Real-world clinical outcomes of cabozantinib (cabo) as a second-line (2L) treatment for advanced hepatocellular carcinoma (aHCC)

Background

Cabo is approved in aHCC patients (pts) with prior sorafenib use. With rapid changes in the first-line (1L) treatment landscape, including use of immuno-oncology (IO) based regimens, this study aims to understand the real-world clinical outcomes of 2L cabo following different 1L therapies in aHCC.

Methods

This retrospective analysis used Komodo Health, Inc. data and included adult pts with aHCC in the US who initiated a 1L regimen between Jan 2017 and Oct 2022 and received 2L cabo. Pts were assigned to 3 cohorts based on 1L therapies: (1) tyrosine kinase inhibitor (TKI) monotherapy (mono), (2) IO+non-IO combination (combo), and (3) IO mono or IO+IO combo. Time to discontinuation (TTD) and time to next treatment or death (TNTD) for 2L cabo were evaluated for each cohort using the Kaplan–Meier method and compared using the log-rank test. Starting dose, dose reduction, and adverse events (AEs) of 2L cabo were described.

Results

160 pts with 2L cabo were included, among whom 68 (42.5%) received 1L TKI, 62 (38.8%) 1L IO+non-IO, and 30 (18.8%) 1L IO mono or IO+IO. Baseline characteristics reflected the real-world aHCC population. The most common regimens were lenvatinib (61.8%) in the TKI cohort, atezolizumab + bevacizumab (91.9%) in the IO+non-IO cohort, and nivolumab (73.3%) in the IO mono or IO+IO cohort. The median (95% CI) TTD for 2L cabo was 3.8 (2.9, 4.9) months in the TKI cohort, 2.9 (2.1, 4.5) in the IO+non-IO cohort, and 2.8 (2.0, 6.8) in the IO or IO+IO cohort. The median (95% CI) TNTD for 2L cabo was 6.5 (5.6, 13.4), 8.6 (5.6, not estimated [NE]), and 10.7 (7.6, NE) months, respectively. The differences in TTD and TNTD among cohorts were not statistically significant (p=0.23 and 0.43, respectively). Among all pts, 74 (46.3%) started cabo at 60 mg and 29 (39.2%) reduced dose, while 60 (37.5%) started at 40 mg and 11 (18.3%) reduced dose. Observed AE rates were as expected with cabo use in previous studies.

Conclusions

This study demonstrates the real-world effectiveness and safety of cabo in 2L aHCC following prior TKIs or IO-based regimens. TNTD, a proxy of progression-free survival, was consistent across different 1L therapies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Exelixis, Inc.

Funding

Exelixis, Inc.

Disclosure

D. Ahn: Financial Interests, Personal, Funding: Bayer, AstraZeneca; Financial Interests, Personal, Other, Travel Accommodations/Expenses: Genentech, Incyte, Exelixis; Financial Interests, Personal, Advisory Board: Exelixis, Genentech, Advanced Accelerator Applications, Incyte; Financial Interests, Personal, Stocks or ownership: Natera. N.J. Park: Financial Interests, Personal, Full or part-time Employment: Exelixis ; Financial Interests, Personal, Full or part-time Employment, Wife: AbbVie; Financial Interests, Personal, Stocks/Shares: Exelixis , AbbVie. M.C. Locker: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks or ownership, Incl ESPP participation: Exelixis, Inc.; Financial Interests, Personal, Proprietary Information, Youngest son has patent pending on clinical trial enrollment: Clinical Trial Enrollment. Z. Zhou: Financial Interests, Personal, Research Funding, am an employee of Analysis Group, an economic consulting firm that is engaged by a variety of clients in the bio-medical arena for a range of services including the study conceptualization, study design and analyses, as well as development of protocols, posters, abstracts, and manuscripts for health economics and outcomes research across many therapeutic areas. Analysis Group's services for each client are confidential and independent of services for other clients. Analysis Group has received consultancy fees from Exelixis to conduct this study.: Analysis Group; Financial Interests, Personal, Advisory Role, I am an employee of Analysis Group, an economic consulting firm that is engaged by a variety of clients in the bio-medical arena for a range of services including the study conceptualization, study design and analyses, as well as development of protocols, posters, abstracts, and manuscripts for health economics and outcomes research across many therapeutic areas. Analysis Group's services for each client are confidential and independent of services for other clients. Analysis Group has received consultancy fees from Exelixis to conduct this study: Analysis Group; Financial Interests, Personal, Full or part-time Employment: Analysis Group. X. Nie: Financial Interests, Personal, Research Funding, I am an employee of Analysis Group, an economic consulting firm that is engaged by a variety of clients in the bio-medical arena for a range of services including the study conceptualization, study design and analyses, as well as development of protocols, posters, abstracts, and manuscripts for health economics and outcomes research across many therapeutic areas. Analysis Group's services for each client are confidential and independent of services for other clients. Analysis Group has received consultancy fees from Exelixis to conduct this study.: Analysis Group; Financial Interests, Personal, Advisory Role, I am an employee of Analysis Group, an economic consulting firm that is engaged by a variety of clients in the bio-medical arena for a range of services including the study conceptualization, study design and analyses, as well as development of protocols, posters, abstracts, and manuscripts for health economics and outcomes research across many therapeutic areas. Analysis Group's services for each client are confidential and independent of services for other clients. Analysis Group has received consultancy fees from Exelixis to conduct this study.: Analysis Group; Financial Interests, Personal, Full or part-time Employment: Analysis Group. T. Wang: Financial Interests, Personal, Research Funding, I am an employee of Analysis Group, an economic consulting firm that is engaged by a variety of clients in the bio-medical arena for a range of services including the study conceptualization, study design and analyses, as well as development of protocols, posters, abstracts, and manuscripts for health economics and outcomes research across many therapeutic areas. Analysis Group's services for each client are confidential and independent of services for other clients. Analysis Group has received consultancy fees from Exelixis to conduct this study.: Analysis Group; Financial Interests, Personal, Advisory Role, I am an employee of Analysis Group, an economic consulting firm that is engaged by a variety of clients in the bio-medical arena for a range of services including the study conceptualization, study design and analyses, as well as development of protocols, posters, abstracts, and manuscripts for health economics and outcomes research across many therapeutic areas. Analysis Group's services for each client are confidential and independent of services for other clients. Analysis Group has received consultancy fees from Exelixis to conduct this study.: Analysis Group; Financial Interests, Personal, Full or part-time Employment: Analysis Group. S. Yu: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks or ownership: Exelixis, Inc.