Are you categorically using lenvatinib over sorafenib for unresectable HCC in the absence of contraindications?

I have done that is recent patients, yes.

I am doing it because "on paper" I see better PFS and better ORR, of course in addition to the non-inferiority when compared to sorafenib in the randomized trial that is now published.

However, I am building experience with respect to tolerance in my particular patient population who tend to be more of the less favorable PS and liver reserve compared to the phase III study population.

I have been also starting in some patients at a lower dose and then building it up.

The REFLECT trial, which demonstrated non-inferiority between lenvatinib and sorafenib in terms of survival, demonstrated an improved response rate with lenvatinib. However, this study enrolled a select patient population, with less than 50% of their liver involved and with good liver function. Thus, I do not uniformly choose lenvatinib over sorafenib as lenvatinib has less data in the types of HCC patients I typically see who have more liver burden and potentially worse liver function than what was seen in the REFLECT trial. In addition, there are differences in the toxicity profile - with higher rates of hypothyroidism and hypertension more common in the lenvatinib population. Thus, I believe it is still a case-by-case basis regarding whi...

To play devil's advocate, I will say no.

While numerically the PFS and ORR may appear higher than Sorafenib, the study was not powered for superiority, thus, one can only truly state that Lenvatinib is not inferior to Sorafenib, not equal.

In regards to ORR observed with Lenvatinib, I do not know what can be really made out of it. When you look at the response rates seen in more recent trials with Regorafenib, Cabozantinib, these are much higher than one would expect to see with TKIs.

Lastly, in regards to the approved therapies in the refractory setting, these are all after failure or intolerance to Sorafenib. While one could easily make the reference stating that an individual will likely see the same observed benefit with treatments tha...