Dr. El-Khoueiry on Choosing Between Lenvatinib and Sorafenib in HCC

Anthony B. El-Khoueiry, MD
Published: Tuesday, Jun 11, 2019



Anthony B. El-Khoueiry, MD, associate professor of clinical medicine, Keck School of Medicine, USC Norris Comprehensive Cancer Center, distinguishes between lenvatinib (Lenvima) and sorafenib (Nexavar) in the frontline treatment of advanced hepatocellular carcinoma (HCC).

Choosing between the 2 TKIs is challenging because the phase III REFLECT study, which led to the FDA approval of lenvatinib in the frontline setting, was a noninferiority study. Lenvatinib was successful in demonstrating noninferiority in terms of overall survival compared with sorafenib. The agent also demonstrated a superior progression-free survival (PFS) and overall response rate (ORR). However, PFS and ORR were secondary endpoints of the trial, and it’s difficult to make treatment decisions based on secondary endpoints, says El-Khoueiry.

Nevertheless, lenvatinib is a potent drug that targets VEGF and FGFR, creating a unique mechanism of action, El-Khoueiry says. The higher ORR and longer PFS may make lenvatinib an option for symptomatic patients who need an immediate response or who may not make it to subsequent lines of therapy.

With regards to safety, the 2 TKIs appear to have overlapping toxicities. However, there was higher risk of hypertension with lenvatinib and higher risk of hand-foot syndrome with sorafenib in the REFLECT study. This could be another factor in determining the right TKI to use, El-Khoueiry concludes.
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Anthony B. El-Khoueiry, MD, associate professor of clinical medicine, Keck School of Medicine, USC Norris Comprehensive Cancer Center, distinguishes between lenvatinib (Lenvima) and sorafenib (Nexavar) in the frontline treatment of advanced hepatocellular carcinoma (HCC).

Choosing between the 2 TKIs is challenging because the phase III REFLECT study, which led to the FDA approval of lenvatinib in the frontline setting, was a noninferiority study. Lenvatinib was successful in demonstrating noninferiority in terms of overall survival compared with sorafenib. The agent also demonstrated a superior progression-free survival (PFS) and overall response rate (ORR). However, PFS and ORR were secondary endpoints of the trial, and it’s difficult to make treatment decisions based on secondary endpoints, says El-Khoueiry.

Nevertheless, lenvatinib is a potent drug that targets VEGF and FGFR, creating a unique mechanism of action, El-Khoueiry says. The higher ORR and longer PFS may make lenvatinib an option for symptomatic patients who need an immediate response or who may not make it to subsequent lines of therapy.

With regards to safety, the 2 TKIs appear to have overlapping toxicities. However, there was higher risk of hypertension with lenvatinib and higher risk of hand-foot syndrome with sorafenib in the REFLECT study. This could be another factor in determining the right TKI to use, El-Khoueiry concludes.



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