The Phase III APOLLO trial, presented at the European Society of Medical Oncology (ESMO) Congress 2024, revealed promising results for the combination of anlotinib and penpulimab as a first-line treatment for advanced hepatocellular carcinoma (aHCC). The study, involving 649 patients, demonstrated significant improvements in both progression-free survival (PFS) and overall survival (OS) compared to sorafenib, a standard treatment for aHCC. This combination offers a potential new option for patients facing this aggressive cancer.
Improved Survival Outcomes
The APOLLO trial randomized patients in a 2:1 ratio to receive either anlotinib plus penpulimab (n=423) or sorafenib (n=212). The results showed a marked improvement in PFS for the combination arm, with a median PFS of 6.9 months compared to 2.8 months for sorafenib (p<0.0001). Similarly, the combination therapy led to an improved OS, with a median of 16.5 months versus 13.2 months for sorafenib (p=0.0012). These findings suggest a clinically meaningful benefit for patients with aHCC.
Anlotinib and Penpulimab Mechanism of Action
Anlotinib, marketed as Focus V by Chia Tai Tianqing Pharmaceutical, is a multi-kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptors (FGFR), and platelet-derived growth factor receptors (PDGFR). This broad inhibition effectively suppresses tumor angiogenesis. Penpulimab, developed by Akeso, is a programmed cell death protein 1 (PD-1) checkpoint inhibitor that enhances the immune system's ability to fight cancer cells. The combination of these two agents provides a dual approach by targeting both tumor growth and immune evasion.
Safety and Tolerability
An important aspect of the APOLLO trial was the manageable safety profile of the anlotinib and penpulimab combination. The study reported fewer treatment-related adverse events (TRAEs) in the combination arm compared to sorafenib. This is a notable advantage, as the tolerability of a treatment significantly impacts patient adherence and quality of life.
Competition in the aHCC Treatment Landscape
While the anlotinib and penpulimab combination shows promise, it enters a competitive landscape. Roche's Tecentriq (atezolizumab) in combination with bevacizumab has emerged as a first-line standard of care for aHCC. The IMbrave150 trial demonstrated that Tecentriq plus bevacizumab significantly improved median PFS compared to sorafenib alone (6.8 versus 4.3 months, p<0.001). Despite the competition, the APOLLO trial results position anlotinib and penpulimab as a viable alternative, particularly given its favorable safety profile.
Implications for Future Treatment Strategies
The APOLLO trial's success underscores the potential of combining tyrosine kinase inhibitors (TKIs) with immune checkpoint inhibitors in treating aHCC. These findings may influence future clinical trials and treatment guidelines, potentially leading to improved outcomes for patients with advanced liver cancer.
