A phase III clinical trial conducted across 12 hospitals in China has revealed that the combination of apatinib with drug-eluting bead transarterial chemoembolization (DEB-TACE) significantly improves outcomes for patients with unresectable hepatocellular carcinoma (uHCC). The study, published in Nature, highlights the potential of this combined approach to extend progression-free survival (PFS) in a challenging patient population.
The trial enrolled patients with uHCC who were ineligible for palliative surgery or radiotherapy, and who had recurrence or metastasis confirmed through histopathology or cytology. Participants were randomized to receive either DEB-TACE alone or DEB-TACE in combination with apatinib. Apatinib, an oral tyrosine kinase inhibitor targeting VEGFR-2, was administered orally at 500mg once daily, starting 3-5 days post-DEB-TACE. Dosing adjustments were made based on adverse events.
The primary endpoint of the study was PFS. Secondary endpoints included overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Safety and tolerability were also closely monitored. The study's rigorous design included computerized central randomization and assessment of treatment efficacy using mRECIST criteria.
Improved Progression-Free Survival
The results demonstrated a statistically significant improvement in PFS for the DEB-TACE plus apatinib group compared to DEB-TACE alone. The estimated median PFS for DEB-TACE + apatinib was approximately 9 months, versus around 6 months for DEB-TACE. This indicates that the addition of apatinib to DEB-TACE can delay disease progression in patients with uHCC.
Safety and Tolerability
While apatinib is associated with known adverse events (AEs), such as hypertension and hand-foot syndrome, the study reported that these were manageable through symptomatic treatment and dose adjustments. The ability to manage these AEs is crucial for maintaining treatment adherence and maximizing the potential benefits of the combination therapy.
Implications for Clinical Practice
The findings from this phase III trial suggest that the combination of apatinib and DEB-TACE represents a promising treatment strategy for patients with uHCC. The improved PFS observed in the study could translate to better clinical outcomes and quality of life for these patients. Further research is warranted to explore the optimal sequencing and duration of treatment with apatinib in combination with DEB-TACE.
