A pivotal phase 3 trial, published in The Lancet on May 9, 2025, revealed that anlotinib combined with penpulimab significantly extends survival in patients with unresectable hepatocellular carcinoma (HCC).

This discovery offers hope for a disease with limited first-line treatment options. “The APOLLO trial, conducted across 79 centers in China, marks a potential shift in HCC therapy,” the investigators reported.

The study, involving 649 patients, compared anlotinib plus penpulimab against sorafenib, a standard treatment.

As per the findings, “Median progression-free survival (PFS) reached 6.9 months with the combination, compared to 2.8 months for sorafenib (hazard ratio [HR] 0.52, p<0.0001).”

“Overall survival (OS) was also prolonged, at 16.5 months versus 13.2 months (HR 0.69, p=0.0014),” the data showed.

“Anlotinib plus penpulimab significantly improved progression-free survival and overall survival,” the study added.

This dual therapy outperformed sorafenib, a tyrosine kinase inhibitor used for over a decade. The trial’s scale and robust outcomes underscore its breakthrough potential.

Anlotinib, a multi-kinase inhibitor, targets tumor angiogenesis by blocking vascular endothelial growth factor receptors.

Penpulimab, an anti-PD-1 antibody, boosts the immune system to attack cancer cells.

“The combination’s safety profile was manageable, though hypertension and platelet count decreases were notable,” the trial data indicated.

Serious adverse events occurred in 21% of the combination group versus 9% for sorafenib. “Treatment-related deaths were minimal,” the team commented, underscoring the therapy’s tolerability.

Penpulimab plus anlotinib showed early promise as a first-line treatment for uHCC, with encouraging efficacy and safety results in a 2021 Frontiers in Oncology study.

The mechanism is straightforward yet powerful: anlotinib starves tumors by inhibiting blood vessel growth, while penpulimab removes cancer’s immune evasion shield, the Lancet study explained.

“The therapy may challenge current standards, like atezolizumab plus bevacizumab,” the authors proposed.

The study underscores the need for innovative combinations in HCC, where survival rates remain low, the team emphasized. Future trials will explore optimal dosing and global applicability.

This research paves the way for improved outcomes in HCC, offering hope to millions battling this aggressive cancer with limited therapeutic options.