Potential new treatment approach for intermediate-stage hepatocellular carcinoma

Abstract

The addition of lenvatinib and pembrolizumab to transarterial chemoembolization (TACE) significantly improved progression-free survival (PFS) in comparison with TACE alone for patients with intermediate-stage hepatocellular carcinoma (HCC) according to interim results of the prospective, phase 3 LEAP-012 study.¹

The lead author of the study, Josep M. Llovet, MD, PhD, director of the Liver Cancer Program and professor of medicine in the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai in New York, presented the results at the 2024 congress of the European Society for Medical Oncology in September.

At a median time of 25.6 months (from randomization to the data cutoff), the median PFS was 14.6 months for patients treated with the addition of lenvatinib and pembrolizumab to TACE and 10.0 months for patients treated with TACE alone, with a hazard ratio of 0.66 (95% CI, 0.51–0.84; p = .0002).

The finding indicates that the prespecified significant improvement in the PFS endpoint of the study was met. No significant improvement in overall survival (OS) was found, but the data are considered immature at this interim analysis.

Grade 3–5 treatment-related adverse events occurred in 71.3% of patients treated with lenvatinib and pembrolizumab plus TACE and in 31.5% of patients treated with TACE alone, and they led to treatment discontinuation in 8.4% and 1.2% of patients, respectively.

Commenting on the study, Kenneth K. Tanabe, MD, professor of surgery at Harvard Medical School and chief of the Division of Oncologic and Gastrointestinal Surgery at Massachusetts General Hospital, says that the findings suggest that lenvatinib and pembrolizumab plus TACE could be a new treatment approach for HCC in the future, but it is “too early to say with any degree of certainty.”

He notes the significantly greater toxicity with the addition of lenvatinib and pembrolizumab to TACE and points to several unknowns that still need answers. First, he questions the benefit of adding pembrolizumab to this regimen considering prior data from the LEAP-002 study that showed no benefit from adding pembrolizumab to lenvatinib in comparison with lenvatinib alone for advanced HCC.²

Also left unanswered, he says, is whether giving TACE alone followed by lenvatinib (sequential administration) at the time of disease progression would yield equivalent OS to that achieved with TACE alone despite the inferior PFS.

“This is not practice changing at this time,” he says, but he urges oncologists to “stay tuned to this channel.”

The LEAP-012 trial included 480 patients with HCC randomized 1:1 to lenvatinib (12 mg for a body weight ≥60 kg and 8 mg for a body weight <60 kg) and pembrolizumab (400 mg) or a placebo for up to 2 years. All patients in both groups received TACE, with the first administration occurring 2–4 weeks after the start of systemic treatment. Patients received up to a maximum of two treatments per tumor (or four total), with the number of treatments not to exceed one per month.^{1, 3}