Comprehensive discussion on the real-world applications of first-line lenvatinib therapy in advanced HCC followed by its potential in combination with TACE.
Josep Llovet, MD: Amit, do you want to talk about your experience with lenvatinib? You produced a paper in the United States.
Amit Singal, MD: We did a real-world study contributing to the data on the real-world effectiveness of lenvatinib. When you pull these experiences together, it gives us a sense of how lenvatinib does in different clinical settings, which helps address some of these questions of viral vs nonviral radiology and expanded use. These phase 3 clinical trials are well-selected patient populations, so it helps us determine the efficacy of those drugs in that select patient population. In clinical practice, we see expansion of these patient populations and whom we want to use, and we don’t have other effective therapies. Most notably, for example, in Child-Pugh B patients. This was a retrospective study that looked at multiple practices in the United States and saw how lenvatinib was being used, as well as the effectiveness of lenvatinib in those different patient populations. In this study, we had a substantial proportion of patients who were Child-Pugh B at baseline, which was notable. We even saw lenvatinib being used and many patients with BCLC [Barcelona Clinic Liver Cancer] stage B disease. We were receiving lenvatinib as first-line therapy.
In brief, what we saw was that the effectiveness of lenvatinib was similar to, or even slightly higher than, what we saw in the REFLECT trial, going to back to your point of feeling more comfortable using lenvatinib in clinical practice. We saw continued effectiveness across different subgroups, whether it was viral vs nonviral radiology, whether it was Child-Pugh A or Child-Pugh B. We saw a small decrease in effectiveness in Child-Pugh B, but I was surprised at the consistency of the effectiveness across all these subgroups. This gives us important data. When we apply this to our patient practice, we can feel comfortable that these results from the REFLECT trial and now even LEAP-002 will apply to our patients in clinical practice. They also gives us some comfort if we were thinking about this in expanded patient populations that were not included in the REFLECT trial. For example, the REFLECT trial excluded patients with greater than 50% liver involvement, excluded patients with main portal vein invasion, and excluded patients with Child-Pugh B disease. These were all included in these real-world effectiveness studies, and we see that lenvatinib is effective in these expanded patient populations.
Josep Llovet, MD: Very good. Do you want to say something?
Katie Kelley, MD: We’ll come back to this later, but what dose do you use for starting in Child-Pugh B?
Amit Singal, MD: Across the board, we typically approach TKIs [tyrosine kinase inhibitors] by starting with reduced dose. That’s not the label, but we start with reduced dose. We then follow the patient. If they tolerate, then we ramp up. That’s our way of keeping patients on therapy. We’ve done that since sorafenib, and we’ve continued this with lenvatinib. I practiced in the United States, where most of our patients are a healthy weight. We start with a dose of 8 mg. If we’re in a Child-Pugh B patient population, we may even start at 4 mg and then ramp up.
Josep Llovet, MD: Final note on lenvatinib in the LEAP-002 objective response. Varices are 17%; modified varices are close to 25%. At this point, as a single agent, it’s the strongest drug in hand. Arndt, do you want to talk about the LAUNCH trial from China published in JCO [Journal of Clinical Oncology], which was TACE [transarterial chemoembolization] plus lenvatinib. You’re familiar with it.
Arndt Vogel, MD: It’s an interesting study looking at the combination of TACE plus lenvatinib in patients with advanced disease. All the phase 3 studies have been published in intermediate stage. Here the majority of patients had extrahepatic spread or vascular infiltration. What they observed is interesting, that the efficacy of TACE can be increased by adding lenvatinib. Response, PFS [progression-free survival] and overall survival, was improved. Having said what we did in the beginning, that we should consider systemic therapies earlier, it doesn’t fit in to the time. [Regarding] the median overall survival, even with the combination it was around 17 months if I remember correctly. As we just said, we have a 19-month effective lenvatinib alone in the advanced population. It’s interesting, but it’s not practice changing.
Josep Llovet, MD: I completely agree. These trials in this case were mostly Chinese centers, right?
Arndt Vogel, MD: Hepatitis B...
Josep Llovet, MD: It has to be used in the West in order to be applied here.
Transcript edited for clarity.