LEAP-002 Trial of Lenvatinib in uHCC Misses Co-Primary End Points

Ghassan K. Abou-Alfa, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the LEAP-002 study (NCT03713593) of pembrolizumab (Keytruda) plus lenvatinib (Lenvima) vs lenvatinib alone in patients with unresectable hepatocellular carcinoma (uHCC).

The global, randomized, double-blind, phase 3 LEAP-002 examined the use of lenvatinib in the first-line for patients with uHCC.

According to Abou-Alfa, the trial failed to meet its co-primary end points of progression-free survival (PFS) and overall survival (OS). However, the trial did demonstrate trends toward improved OS and PFS among those who received the combination regimen.

Transcription:

0:08 | We were all excited about the LEAP-002 study which evaluated the combination of pembrolizumab plus lenvatinib, an anti PD-1 plus anti-EGFR vs lenvatinib as a standard of care as a TKI. It is a drug that we all use and have used. That study carried on with high anticipation because of the concept of combining a checkpoint inhibitor plus an anti-TKI or specifically, an anti-MGF, per se, especially because the phase 1B study of the combination was promising within the limitation of it being phase 1B study. It had been a median survival of 22 months. However, the LEAP-002 study of pembrolizumab plus lenvatinib vs lenvatinib was negative.

1:08 | It showed that the median survival did not differ much between the lenvatinib plus pembrolizumab arm which was a total of 21 months vs lenvatinib at 19 months. If anything, the hazard ratio did not favor that improved survival that we're all looking for which was 0.84. The question is why.

1:33 | Understandably, that could be the design of the study. It could be, did people get second-line therapy after the lenvatinib? If anything, yes, at least a certain percentage of them, not all of them, but about 20% or more did receive second-line checkpoint inhibitors. Number 3 is, could the population be in particular regard to that. A very important point over here, that the hepatitis B patients were close to at about 50%, where we know that checkpoint inhibitors favor best regard to the patients with hepatitis B.