PFS, OS in unresectable HCC prolonged with anlotinib plus penpulimab

In the treatment of patients with unresectable hepatocellular carcinoma (HCC), anlotinib plus pepulimab appears to significantly increase progression-free survival (PFS) and overall survival (OS) compared with sorafenib, as shown in the results of the phase III APOLLO study conducted in China.

APOLLO included 649 Chinese adult patients (median age 57 years, 85 percent male) with unresectable HCC, no previous systemic therapy, and an ECOG performance status of 0 or 1. These patients were randomly assigned to receive anlotinib (10 mg orally once daily on days 1–14) plus penpulimab (200 mg intravenously on day 1) (n=433) or sorafenib alone (400 mg orally twice daily) (n=216) every 3 weeks.

The co-primary endpoints were PFS and OS, assessed in the intention-to-treat population. Safety was evaluated in all participants who received at least one dose of the study drug and had at least one recorded safety assessment.

The intention-to-treat population comprised 636 patients for the final PFS analysis and 649 for the interim OS analysis. The median follow-up was 6.2 months with the anlotinib plus penpulimab group and 4.2 months with the sorafenib group for PFS, and 15.3 and 14.5 months, respectively, for OS.

Compared with sorafenib, anlotinib plus penpulimab resulted in significantly longer PFS (median, 6.9 vs 2.8 months; hazard ratio [HR], 0.52, 95 percent confidence interval [CI], 0.41–0.66; p<0.0001) and OS (median, 16.5 vs 13.2 months; HR, 0.69, 95 percent CI, 0.55–0.87; p=0.0014).

The most common grade 3 or worse treatment-related adverse events (AEs) were hypertension (17 percent with anlotinib plus penpulimab vs 10 percent with sorafenib) and decrease in platelet count (9 percent vs 6 percent).

Treatment-related serious AEs occurred in 21 percent of patients in the anlotinib plus penpulimab group and in 9 percent in the sorafenib group. There were three treatment-related deaths documented overall—the first due to an upper gastrointestinal haemorrhage in the anlotinib plus penpulimab group, the second due to hepatic failure, and the third due to an unknown cause in the sorafenib group.