Outcomes of First Versus Second-Line Hepatic Artery Infusion Chemotherapy in Unresectable Intrahepatic Cholangiocarcinoma.

Background: Hepatic artery infusion chemotherapy (HAIC) has shown survival benefits in unresectable intrahepatic cholangiocarcinoma (IHC). The optimal timing of HAIC remains uncertain. This study compares outcomes with HAIC when used as first-line treatment compared with as second-line treatment in patients with advanced IHC.

Methods: A total of 722 patients with biopsy-proven IHC treated from 2000 to 2018 were evaluated. Patients undergoing upfront resection or with metastatic disease beyond regional lymph nodes were excluded. Overall survival (OS) was calculated from the date of diagnosis using Kaplan-Meier methods. To assess the impact of timing of HAIC on survival, multi-state models using parametric Cox regression and separate cause-specific hazard models were used to estimate mean survival time from diagnosis.

Results: A total of 336 patients eligible for HAIC were analyzed: 137 received first-line HAIC and 199 received first-line systemic chemotherapy (SYS). The median OS of all patients was 22 months (95% confidence interval [CI] 20-25), and HAIC given at any time was associated with reduced all-cause mortality by 34% (hazard ratio [HR] 0.66; 95% CI 0.52-0.84). Of 199 patients who received first-line SYS, 59 received second-line HAIC, 73 received second-line SYS, and 67 did not receive further treatment. Multi-states analyses revealed that first-line HAIC was associated with a mean survival time of 33 months, compared with 36 months for second-line HAIC and 22 months for those who received second-line SYS.

Conclusion: HAIC is associated with a survival benefit whether administered in the first-line or second-line setting, supporting its use as an effective treatment option in unresectable IHC.