First-Line Anlotinib Plus Penpulimab for Patients With Unresectable Hepatocellular Carcinoma
According to results from the phase 3 APOLLO trial, first-line anlotinib plus penpulimab significantly improved outcomes compared to anlotinib plus sorafenib among patients with unresectable hepatocellular carcinoma.
“Immunotherapy combinations have revolutionised the therapeutic landscape of advanced hepatocellular carcinoma, but not all yield a significant overall survival benefit, underscoring the need for novel effective agents,” stated Jian Zhou, MD, Zhongshan Hospital, Fudan University, Shanghai, China, and coauthors. “Anlotinib plus penpulimab has demonstrated encouraging activity and safety in a phase 2 study.”
In this open-label, parallel-controlled trial, 649 patients were randomized on a 2-to-1 basis to receive 10 mg of anlotinib once daily on days 1 through 14 plus either 200 mg of penpulimab (n = 433) or 400 mg of sorafenib (n = 216) once every 3 weeks, stratified based on macrovascular invasion or extrahepatic metastasis, α-fetoprotein concentration, and performance status. Primary end points included progression-free survival (PFS) and overall survival (OS). A key secondary end point was safety.
At analysis, the second interim OS was 15.3 months in the penpulimab arm and 14.5 months in the sorafenib arm. Median PFS was 6.9 months in the penpulimab arm and 2.8 months in the sorafenib arm (hazard ratio [HR] 0.69; 95% confidence interval [CI], 0.41 to 0.66; P < .0001) and median OS was 16.5 months and 13.2 months (HR 0.69; 95% CI, 0.55 to 0.87; P = .0014), respectively.
The most common grade ≥3 treatment-related adverse events included hypertension and decreased platelet count. Serious treatment-related adverse events occurred in 21% of patients in the penpulimab arm and 9% of patients in the sorafenib arm. One treatment-related death occurred in the penpulimab arm due to upper gastrointestinal hemorrhage and 2 treatment-related deaths occurred in the sorafenib arm due to hepatic failure and unknown cause.
“Anlotinib plus penpulimab significantly improved [PFS] and [OS] versus sorafenib in unresectable [hepatocellular carcinoma] and might be a new first-line option,” concluded Dr Zhou et al. “These findings require verification in other regions of the world.”
Source:
Zhou J, Bai L, Luo J, et al. Anlotinib plus penpulimab versus sorafenib in the first-line treatment of unresectable hepatocellular carcinoma (APOLLO): A randomised, controlled, phase 3 trial. Lancet Oncol. Published online: May 8, 2025. doi: 10.1016/S1470-2045(25)00190-1
