Treatment outcomes of advanced hepatocellular carcinoma in real-life practice : chemotherapy versus Multikinase inhibitors

Abstract

Multikinase inhibitors (MKIs) are the main treatment of advanced hepatocellular carcinoma (aHCC). Nevertheless, the accessibility to MKIs in developing countries is limited. Chemotherapy (CMT) which is cheaper than MKIs may be an option for the patients. Therefore, this study aimed to compare the clinical effectiveness of the CMT with MKIs in the first-line treatment of aHCC in the real-life practice. A retrospective cohort of aHCC using the real-world practice data from 3 medical schools and 1 regional hospital was conducted. The patients who received Doxorubicin, FOLFOX, or Sorafenib as first-line treatment between 2013–2019 were included in this study. Multiple imputation using the chain equation was applied to solve the missing data of covariables. The treatment effect model using Weight-adjusted-censoring inverse-probability-weighted regression adjustment (WAC-IPWRA) and IPWRA estimator was applied to time-to-event and binary outcomes, respectively. The results from the imputed data and listwise deletion were compared. A total of 673 patients were included in the estimation of relative treatment effects among Sorafenib (n=383), Doxorubicin (n=168), and FOLFOX (n=122). The treatment effect model, WAC-IPWRA estimators showed that Doxorubicin had the longest overall survival (OS) followed by Sorafenib and FOLFOX with the median OS of 23.3, 12.2, and 10.6 months, respectively. Conversely, the median progression-free survival (PFS) was the longest in Sorafenib followed by Doxorubicin and FOLFOX with the median PFS of 6.8, 5.6, and 4.8 months, respectively. Furthermore, the disease control rate was not much different in Sorafenib and Doxorubicin, but it was the lowest in FOLFOX. Finally, serious adverse events were present more in FOLFOX than Doxorubicin and Sorafenib. The results between the imputed data and listwise deletion were very closed in point estimate. Only the precision of estimation, in which the multiple imputation tended to have less standard errors when compared to the listwise deletion method. Even though the lower border of 95% confidence interval of difference of median OS crossed the non-inferior margin, the point estimate was not. Thus, we could not demonstrate the non-inferiority of CMT to Sorafenib. Therefore, further observational cohort studies with a larger sample size are needed to conclude that CMT can solve this clinical unmet need problem.