Why carry out this study?

Cabozantinib (a once-daily oral tyrosine kinase inhibitor with targets including MET, AXL and vascular endothelial growth factor [VEGF] receptors) and ramucirumab (a monoclonal antibody specific for VEGF receptor-2, administered every 2 weeks by intravenous infusion) are approved for the second-line (2L) treatment of hepatocellular carcinoma (HCC) after sorafenib; however, ramucirumab is restricted to use in patients with serum alpha-fetoprotein (AFP) levels of 400 ng/mL or above.

No clinical trials have compared cabozantinib and ramucirumab directly in patients with HCC and elevated serum AFP. This analysis compared 2L cabozantinib and ramucirumab in patients with HCC and serum AFP of 400 ng/mL or above using a matching-adjusted indirect comparison (MAIC) approach.

What was learned from this study?

In 2L HCC populations matched for prior therapy and clinically relevant baseline characteristics, cabozantinib significantly prolonged median (95% CI) progression-free survival compared with ramucirumab (5.5 [4.6–7.4] months vs. 2.8 [2.7–4.1] months; p = 0.016); overall survival (median [95% CI]) was not significantly different for cabozantinib (10.6 [9.5–17.3] months) and ramucirumab (8.7 [7.3–10.8] months) (p = 0.104).

Discontinuation rates resulting from treatment-related adverse events were not significantly different for the matching-adjusted cabozantinib population and the ramucirumab population (log odds ratio [95% CI] for cabozantinib vs. ramucirumab, 1.16 [−0.89, 3.20]; p = 0.271).

In the absence of direct comparative trial data, this MAIC analysis may help to inform individualized clinical decision-making with respect to 2L treatment for patients with HCC and elevated serum AFP who have received prior sorafenib.