DR LOVE: Maybe we can talk a little bit about TKIs and anti-VEGF therapy in HCC. If you could, maybe go through a little bit in terms of where we started, in terms of sorafenib.

DR EL-KHOUEIRY: Okay. So with sorafenib there were 2 international trials that established this as the standard first-line systemic therapy for advanced hepatocellular carcinoma. And just to make sure that we’re speaking the same language, when we say advanced hepatocellular carcinoma, we’re talking really about patients who generally have either extrahepatic metastases or have liver-limited disease with vascular invasion, traditionally portal vein invasion — this is macroscopic, so visible on a scan — or patients who have liver-limited disease and have failed local-regional modalities, so they have progressed both transarterial chemoembolization.

If you use the Barcelona Clinic Liver Cancer staging system, these are patients with BCLC Stage C, or B who’ve progressed on local-regional therapy. That’s the traditional population. Both the SHARP trial and the Asia-Pacific trial showed a statistically and clinically significant improvement in overall survival with sorafenib compared to placebo, with a hazard ratio in the range of 0.6, so about a 40% risk reduction for death. This was consistent data across 2 trials and established sorafenib as the standard of care.

Now of note, most of us who treat this disease realize that the chance of a radiologic response with sorafenib is quite minimal. We’re talking about 2% to 3% range. But nonetheless there is a cytostatic effect and improvement in survival.

Efficacy of sorafenib and integration of the recently FDA-approved multikinase inhibitor regorafenib into the treatment algorithm for advanced hepatocellular carcinoma (HCC)

Immune checkpoint inhibitors in the management of HCC: Biologic rationale and emerging data

Activity and tolerability of lenvatinib for patients with unresectable HCC

Management of local-regional disease