VEGF Inhibitors Improve Survival Outcomes in Patients with Liver Metastases across Cancer Types-A Meta-Analysis

Jordan W Conway; Jorja Braden; Serigne N Lo; Richard A Scolyer; Matteo S Carlino; Alexander M Menzies; Georgina V Long; Ines Pires da Silva

doi:10.3390/cancers15205012

VEGF Inhibitors Improve Survival Outcomes in Patients with Liver Metastases across Cancer Types-A Meta-Analysis

Cancers (Basel). 2023 Oct 16;15(20):5012. doi: 10.3390/cancers15205012.

Authors

Jordan W Conway^{1

2

3}, Jorja Braden^{1

2

3}, Serigne N Lo^{1

2}, Richard A Scolyer^{1

2

3

4

5}, Matteo S Carlino^{1

2

6}, Alexander M Menzies^{1

2

7

8}, Georgina V Long^{1

2

3

7

8}, Ines Pires da Silva^{1

2

3

6}

Affiliations

¹ Melanoma Institute Australia, The University of Sydney, 40 Rocklands Rd, North Sydney, NSW 2065, Australia.
² Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2050, Australia.
³ Charles Perkins Centre, The University of Sydney, Sydney, NSW 2050, Australia.
⁴ Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
⁵ NSW Health Pathology, Sydney, NSW 2099, Australia.
⁶ Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, NSW 2148, Australia.
⁷ Royal North Shore Hospital, Sydney, NSW 2065, Australia.
⁸ Mater Hospital, Sydney, NSW 2060, Australia.

Abstract

Background: Liver metastases are associated with poor prognosis across cancers. Novel treatment strategies to treat patients with liver metastases are needed. This meta-analysis aimed to assess the efficacy of vascular endothelial growth factor inhibitors in patients with liver metastases across cancers.

Methods: A systematic search of PubMed, Cochrane CENTRAL, and Embase was performed between January 2000 and April 2023. Randomized controlled trials of patients with liver metastases comparing standard of care (systemic therapy or best supportive care) with or without vascular endothelial growth factor inhibitors were included in the study. Outcomes reported included progression-free survival and overall survival.

Results: A total of 4445 patients with liver metastases from 25 randomized controlled trials were included in this analysis. The addition of vascular endothelial growth factor inhibitors to standard systemic therapy or best supportive care was associated with superior progression-free survival (HR = 0.49; 95% CI, 0.40-0.61) and overall survival (HR = 0.83; 95% CI, 0.74-0.93) in patients with liver metastases. In a subgroup analysis of patients with versus patients without liver metastases, the benefit with vascular endothelial growth factor inhibitors was more pronounced in the group with liver metastases (HR = 0.44) versus without (HR = 0.57) for progression-free survival, but not for overall survival.

Conclusion: The addition of vascular endothelial growth factor inhibitors to standard management improved survival outcomes in patients with liver metastasis across cancers.

Keywords: VEGF inhibitor; drug resistance; immunotherapy resistance; liver metastases; meta-analysis; overall survival; progression-free survival; randomized controlled trials.

Publication types

Review

Grants and funding

S.N.L is supported by Melanoma Institute Australia. R.A.S. is supported by a National Health and Medical Research Council of Australia (NHMRC) Investigator Grant (APP2018514). A.M.M. is supported by an NHMRC Investigator Grant, Nicholas and Helen Moore, and Melanoma Institute Australia. G.V.L. is supported by an NHMRC Investigator Grant and the University of Sydney Medical Foundation. I.P.d.S. is supported by the early-career CINSW fellowship. This project was supported by Lady Mary Fairfax Charitable Trust.