The combination of anlotinib (Focus V) and penpulimab is emerging as a potential first-line treatment for advanced hepatocellular carcinoma (aHCC), demonstrating significant improvements in both progression-free survival (PFS) and overall survival (OS) compared to sorafenib. These findings were presented at the European Society of Medical Oncology (ESMO) Congress 2024 from the Phase III APOLLO trial.
APOLLO Trial: Key Findings
The APOLLO trial randomized 649 patients in a 2:1 ratio to receive either the combination of anlotinib and penpulimab (n=423) or sorafenib (n=212). Anlotinib, developed by Chia Tai Tianqing Pharmaceutical, is a multi-kinase inhibitor targeting vascular endothelial, fibroblast, and platelet-derived growth factor receptors, effectively inhibiting tumor angiogenesis. Penpulimab, developed by Akeso, is a programmed cell death protein 1 (PD-1) checkpoint inhibitor.
The study revealed a significant benefit in PFS for the anlotinib plus penpulimab arm, with a median PFS of 6.9 months compared to 2.8 months for sorafenib (p<0.0001). Similarly, OS improved in the combination arm, with 16.5 months versus 13.2 months for sorafenib (p=0.0012). The combination therapy also demonstrated a manageable safety profile, with fewer treatment-related adverse events (TRAEs) compared to sorafenib.
Comparison with Other IO-TKI Combinations
These results are particularly noteworthy considering the previous failure of the LEAP-002 trial, where pembrolizumab (Keytruda) in combination with levantinib did not show a clinically significant benefit. Another IO-TKI combination, camrelizumab and rivoceranib, also presented clinical data from the Phase III CARES-310 trial, showing similar benefits in PFS (5.6 vs 3.7 months, p<0.0001) and OS (22.1 vs 15.2 months, p<0.0001) compared to sorafenib. However, the anlotinib and penpulimab combination appears to have an edge in terms of safety, with fewer TRAEs compared to sorafenib, a benefit not observed with the camrelizumab and rivoceranib combination.
Competition in the First-Line aHCC Landscape
Despite the promising results, the anlotinib and penpulimab combination faces stiff competition, particularly from Roche's atezolizumab (Tecentriq) with bevacizumab, which has become a first-line standard-of-care in aHCC. This approval was based on a Phase III trial demonstrating a significant improvement in median PFS compared to sorafenib alone (6.8 vs. 4.3 months, p<0.001) and a relatively indifferent safety profile. GlobalData forecasts Tecentriq sales to reach $980 million across major markets by 2029.
While the anlotinib and penpulimab combination shows strong performance, it is not the first IO-TKI combination to demonstrate tangible results and will face significant challenges in displacing Tecentriq from its leading position in the first-line treatment of aHCC.
