Arndt Vogel, MD, PhD: Reimbursement is really a problem in the future. At the moment, of course if a drug is not approved, at least in Europe or in Germany, we have to ask the health insurance whether they would reimburse the cost of the treatment. In the future I think it will be more difficult, because depending on the labor of a certain drug, we might be forced to use our first-line therapy in light of the drugs we would like to use in second line. Because most of these drugs have been tested following sorafenib treatment, which might force us to use sorafenib first and then any of the other drugs that are or will be approved in second line.

And this is a reimbursement issue because when we start with lenvatinib, and we do not have any data for cabozantinib, ramucirumab, or immunotherapy, after lenvatinib we might get problems with the reimbursement. And I think there’s a problem that really depends on different countries. In Germany we can use lenvatinib in first line. Sorafenib is approved independent of line of therapy, so we could use sorafenib in second line. And then after sorafenib failure we could use any other drug that has been tested after sorafenib failure in third line. But this would shift all drugs in further down the line, right? So sorafenib would go to second line, and all the second-line drugs would go to third line. I’m not really sure whether this is the best way to go, and therefore I think it will be really important to understand maybe from real-life data what is the best sequence of drugs we use in HCC.

Masatoshi Kudo, MD, PhD: We don’t have any program of reimbursement after lenvatinib or sorafenib or immunotherapy, because this is a Japanese situation. And in Japan, for example, regorafenib’s clinical trial was after sorafenib, but the indication is only as a secondary agent after first-line systemic therapy. So we expect ramucirumab’s indication is just after first-line systemic therapy. So we do not have any problem.

Transcript Edited for Clarity