Efficacy of Pembrolizumab Plus Lenvatinib for Patients With Advanced HCC

A phase 3, double-blind study compared the efficacy of pembrolizumab plus lenvatinib with lenvatinib alone and found that the combination therapy did not significantly improve overall survival (OS) and progression-free survival (PFS) in patients with advanced hepatocellular carcinoma (HCC).

The trial was conducted by Josep M. Llovet, MD, of the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, and colleagues and published in The Lancet.

The cohort comprised 794 patients older than 18 years who were previously diagnosed with unresectable HCC and Child-Pugh class A liver disease. In addition, they had an Eastern Cooperative Oncology Group performance status of 0 or 1 and had not previously undergone treatment.

Researchers randomly assigned patients to receive a 200 mg dose of pembrolizumab plus lenvatinib or lenvatinib plus placebo every 3 weeks. Of the patients, 395 were given pembrolizumab plus lenvatinib, and 399 received lenvatinib plus placebo. The trial’s primary endpoints were OS and PFS.

The OS for patients who took pembrolizumab plus lenvatinib was 21.2 months (95% CI, 19.0-23.6) compared with 19.0 months for patients prescribed lenvatinib plus placebo (95% CI, 17.2-21.7).

The median PFS for patients given pembrolizumab plus lenvatinib was 8.2 months (95% CI, 6.4-8.4) and 8.0 months for patients who received lenvatinib plus placebo (95% CI, 6.3-8.2).

Investigators found that patients who experienced treatment-related, grade 3-4 adverse effects most often reported hypertension, increased aspartate aminotransferase, and diarrhea. Treatment-related deaths were reported in 4 (1%) patients in the pembrolizumab plus lenvatinib group and 3 (1%) in the lenvatinib alone group.

Dr. Llovet and colleagues recommended that pembrolizumab plus lenvatinib not be added to the standard clinical practice for patients with advanced HCC.

“In earlier studies, the addition of pembrolizumab to lenvatinib as first-line therapy for advanced hepatocellular carcinoma has shown promising clinical activity; however, lenvatinib plus pembrolizumab did not meet prespecified significance for improved overall survival and progression-free survival versus lenvatinib plus placebo,” the researchers concluded.