A recent study indicates that a combination of hepatic arterial infusion chemotherapy (HAIC) with lenvatinib and PD-1 inhibitors shows promising results in treating advanced intrahepatic cholangiocarcinoma (ICC). The research, conducted at Zhongshan People’s Hospital, compared this combination therapy to first-line systemic chemotherapy, revealing improved survival rates and fewer adverse events. These findings suggest a potential new approach to managing this challenging cancer.
The study, a retrospective review of 90 patients treated between July 2020 and January 2023, divided participants into two groups: 51 receiving HAIC plus lenvatinib and PD-1 inhibitor treatment (HAIC+L+P group) and 39 receiving systemic chemotherapy (cisplatin + gemcitabine) (SC group). The results indicated that the HAIC+L+P group experienced notably extended median overall survival (mOS) and progression-free survival (mPFS), along with higher objective response rate (ORR) and disease control rate (DCR), according to both RECIST 1.1 and mRECIST criteria.
Advantages of HAIC
HAIC delivers high concentrations of chemotherapy drugs directly to liver lesions via a catheter inserted into the hepatic artery. This method allows for targeted treatment of diffuse lesions and tumor thrombi, regardless of size or location. "HAIC can concentrate drug concentrations in the liver up to 400 times higher than systemic administration," the study notes, potentially reducing systemic toxicity due to the liver's first-pass effect.
Targeted and Immunotherapy Contributions
Lenvatinib, a tyrosine kinase inhibitor, targets multiple receptors, including VEGFR 1-3 and FGFR 1-4, inhibiting tumor angiogenesis. PD-1 inhibitors enhance the immune response against the tumor. The combination aims to address both local and systemic disease progression, overcoming the limitations of HAIC alone.
Key Findings
The study observed that the HAIC+L+P group experienced fewer treatment-related adverse events (TRAEs) compared to the SC group. Common TRAEs included leukopenia, thrombocytopenia, rash, abdominal pain, nausea, vomiting, decreased appetite, fatigue, elevated ALT levels, elevated AST levels, hypertension, and elevated bilirubin. However, the HAIC+L+P group had lower rates of nausea, vomiting, leukopenia, and thrombocytopenia, though hypertension and elevated ALT/AST levels were more frequent. The number of grade 3-4 adverse events was also lower in the HAIC+L+P group.
Study Limitations
The authors acknowledge several limitations, including the retrospective, single-center design and the potential for selection bias due to treatment choices based on doctor and patient preferences. The relatively short mean follow-up duration in the HAIC+L+P group was also noted. The study calls for prospective, large-sample, randomized controlled trials to validate these findings.
Implications for ICC Treatment
Despite the limitations, the study suggests that combining HAIC with lenvatinib and PD-1 inhibitors may offer a more effective and tolerable treatment option for advanced ICC compared to standard systemic chemotherapy. The results highlight the potential for improved tumor remission rates, increased overall survival, and reduced adverse events, warranting further investigation in larger, prospective trials.
