Josep Llovet, MD: It’s about time to move to second-line [therapy]. I have some slides that I will mention very briefly. Regorafenib showed superiority against placebo in second line in patients who tolerated or progressed to sorafenib. This was a trial that showed a hazard ratio of 0.63 and a median overall survival of 10.6 months for regorafenib This established that it works in group analyses.

Cabozantinib is a multikinase inhibitor with a uniqueness that’s blocking MET signaling. It showed superiority vs placebo, with a median survival of 10.2 months vs around 8 months. In the subgroup analysis, cabozantinib shows more efficacy in patients with extrahepatic spread, macrovascular invasion, and hepatitis B virus infection.

Finally, ramucirumab in the REACH trial was negative. In the subgroup analysis, for patients with AFP [alpha-fetoprotein] of more than 400 ng/mL, the drug was efficacious. In the second trial, REACH-2, [median survival was] 8.5 months; the control arm was 7.3. But in the meta-analysis, that probably captures better population in the second line with an AFP of more than 400 ng/mL—40% of patients in the second line and have of AFP more than 400 ng/mL. The median survival for placebo is 5 months and around 8 months for ramucirumab.

In terms of adverse events, regorafenib has grade 3/4 adverse events in 50% of the population in the second line. Patients who do not tolerate sorafenib have been excluded in the trial. For CELESTIAL, the trial didn’t really publish treatment-related adverse events, but it’s estimated to be 55% or 60%.

Transcript edited for clarity.