The Phase III APOLLO study, presented at ESMO 2024, revealed that the combination of anlotinib and penpulimab significantly improves outcomes in patients with newly diagnosed advanced hepatocellular carcinoma (HCC). The study, conducted entirely in China, compared the combination therapy to sorafenib, a standard treatment for HCC.
The APOLLO study enrolled 648 patients with advanced HCC, randomizing them in a 2:1 ratio to receive either anlotinib plus penpulimab or sorafenib. The patient population primarily consisted of individuals with BCLC stage B disease and Child-Pugh Class A cirrhosis, with a significant proportion having hepatitis B-related cirrhosis (84.3% in the investigational arm and 83.8% in the sorafenib arm).
The dual primary endpoints of the study were progression-free survival (PFS) and overall survival (OS). The results showed a statistically significant improvement in PFS with the anlotinib-penpulimab combination, with a median PFS of 6.9 months compared to 2.8 months with sorafenib (HR=0.3). Similarly, the combination therapy demonstrated a significant improvement in OS, with a median OS of 16.5 months versus 13.2 months for sorafenib (HR=0.69).
"The APOLLO Study met its endpoints of improvements in median progression-free survival and overall survival with the combination of anlotinib and penpulimab, compared to sorafenib, and that it was a relatively well-tolerated agent," the authors concluded.
Regarding safety, the incidence of grade 3 or greater treatment-related adverse events was relatively balanced between the two arms, with approximately 50% of patients in each arm experiencing such events. Common adverse events included hypertension and hematologic toxicities. Notably, the incidence of immune-related adverse events was low (less than 5%).
It's important to consider that a notable percentage of patients received subsequent anticancer therapies (35.8% in the investigational arm and nearly 45% in the sorafenib arm), which could potentially influence the overall survival data. These subsequent therapies included anti-angiogenic treatments and PD-L1 inhibitors.
The APOLLO study suggests that the combination of a tyrosine kinase inhibitor (TKI) and immunotherapy holds promise in HCC treatment. However, previous studies, such as the LEAP-002 and COSMIC-312 trials, have not shown similar benefits with other TKI-anti-PD-1 combinations in different populations. In contrast, the CARES-310 study, conducted predominantly in Asia, demonstrated an impressive median overall survival of 22.1 months with camrelizumab and rivoceranib, another TKI and anti-PD-1 combination.
While the APOLLO study results are encouraging, the fact that it was conducted entirely in China with a predominantly hepatitis B etiology population raises questions about the generalizability of the findings to other populations. Further research is needed to determine whether this combination therapy can be successfully implemented more globally.
