Lenvatinib benefit extends to Child-Pugh B HCC patients

Lenvatinib confers better clinical outcomes than sorafenib in patients with unresectable hepatocellular carcinoma (uHCC) even when their liver function deteriorates to Child-Pugh B after initiation of treatment, according to a post hoc analysis of the REFLECT study.

Lenvatinib is a multiple kinase inhibitor that targets VEGF receptors 1–3, PDGF receptor α, FGF receptors 1–4, RET, and KIT. Lenvatinib has been approved as first-line therapy for uHCC based on primary results of the REFLECT study, which showed that lenvatinib was noninferior to sorafenib for overall survival (OS) in patients with untreated advanced HCC.

“[Although] the treatment landscape for patients with uHCC has recently expanded, … there is an unmet need for effective treatment options in patients with Child-Pugh B liver function,” said the researchers.

The phase III, multicentre, open-label, noninferiority trial randomized patients with uHCC to lenvatinib (12 mg/day for ≥60 kg; 8 mg/day for <60 kg) or sorafenib (400 mg twice daily) in 28-day cycles. The current post hoc analysis looked at treatment outcomes in patients with reduced liver function by stratifying patients based on whether they have progressed to Child-Pugh B or remained as Child-Pugh A during the first 8 weeks of treatment. [ESMO GI 2021, abstract P-78]

In a landmark OS analysis, lenvatinib led to longer OS than sorafenib including in patients with Child-Pugh B. However, outcomes were consistently poorer in patients with Child-Pugh B vs Child-Pugh A regardless of the treatment received. 

Among patients treated with lenvatinib, Child-Pugh B patients had a median OS of 6.8 months (95 percent confidence interval [CI], 2.6–10.3) compared with 13.3 months (95 percent CI, 11.6–16.1) in Child-Pugh A patients. Likewise, median OS was 4.5 months (95 percent CI, 2.9–6.1) vs 12.0 months (95 percent CI, 10.2–14.0) in Child-Pugh B vs Child-Pugh A patients, respectively, in the sorafenib arm.

A landmark analysis of PFS also showed similar findings. In the lenvatinib arm, median PFS was 3.7 months (95 percent CI, 1.8–7.4) in Child-Pugh B patients compared with 6.5 months (95 percent CI, 5.6–7.4) in Child-Pugh A patients. With sorafenib, median PFS was 0.5 months (95 percent CI, 0.1–3.6) vs 3.6 months (95 percent CI, 2.7–3.7) in Child-Pugh B vs Child-Pugh A patients, respectively.

In addition, objective response rate (ORR) was also higher with lenvatinib than sorafenib, with better rates in Child-Pugh A patients than Child-Pugh B patients in each arm (42.9 percent vs 28.3 percent for lenvatinib, and 12.9 percent vs 8.5 percent for sorafenib).

Grade ≥3 treatment-related adverse events occurred more commonly in Child-Pugh A patients than in Child-Pugh B patients in both the lenvatinib arm (3.65 vs 1.41) and the sorafenib arm (3.38 vs 1.71).

“The results indicate that patients with uHCC whose liver function deteriorates to Child-Pugh B after initiation of therapy may continue to receive lenvatinib, and further study of lenvatinib in Child-Pugh B patients with uHCC is warranted,” said the researchers.