Exploring Differences in Survival With Lenvatinib in Recent HCC Trials

Pierre Gholam, MD, associate professor of medicine at Case Western Reserve University School of Medicine, and director of the multidisciplinary hepatobiliary tumor team at University Hospitals Seidman Cancer Center in Cleveland, Ohio, observes the improvements in outcomes with lenvatinib (Lenvima) seen in recent trials of unresectable hepatocellular carcinoma (HCC) compared with the original phase 3 REFLECT trial (NCT01761266).

Gholam explains that in the recent CheckMate 9DW trial (NCT04039607) investigating nivolumab (Opdivo) plus ipilimumab (Yervoy), the majority of patients in the comparator arm received lenvatinib. Single-agent lenvatinib was also the comparator arm vs lenvatinib plus pembrolizumab (Keytruda) in the LEAP-002 trial (NCT03713593). In both trials, the median overall survival (OS) for the comparator arm was several months longer than expected based on OS from the REFLECT trial that led to its approval in 2018.

Though the different trials cannot be directly compared, Gholam says this shows how the context of using a particular drug can change the outcome for patients. The previous trials were run when there were few other options available besides lenvatinib and sorafenib (Nexavar), whereas contemporary trials were run when multiple other options are available in the first- and second-line setting. The more recent trials show that patients may derive greater benefit from these therapies now than when they were initially available.

TRANSCRIPTION

0:10 | The CheckMate 9DW trial was essentially a study of nivolumab plus ipilimumab, compared to a comparator arm, which was dealer's choice, typically either lenvatinib or sorafenib. I think 85% of patients who participated in that particular trial ended up receiving lenvatinib. And if you look at the OS, this was a positive study, of course, which resulted in ipilimumab/nivolumab becoming an approved first-line treatment in unresectable HCC.

0:50 | The bottom line here is that in CheckMate 9DW again, there was a very significant…increase in the OS related to lenvatinib, which was 85% of the comparator arm. There you're looking at 20.6 months for the lenvatinib arm vs 23.7 months for nivolumab/ipilimumab. You're looking at a survival rate that was almost in the same range as you saw it in the lenvatinib/pembrolizumab LEAP-002 trial.

1:39 | I only mention this to say that depending on what context you may be using a particular drug, and in this particular case, lenvatinib, in the more contemporary era where you have extensive options, both in first line and second line, you might derive a greater benefit from that setting of care than you would…in 2017 or 2018 when sorafenib and lenvatinib were really the only 2 first-line treatments available.