TKI plus ICI versus ICI alone in high tumor burden hepatocellular carcinoma: a retrospective cohort study

Combination regimens and monotherapy are both employed in the treatment of hepatocellular carcinoma (HCC). However, the optimal combination regimen for specific scenarios remains unclear. Therefore, our aim is to identify predictors of survival and determine whether combination therapy or monotherapy provides better outcomes for HCC patients.

From August 2015 to July 2020, a total of 129 unresectable HCC patients receiving immune checkpoint inhibitors (ICI) were recruited. Patients were divided into high tumor burden and low tumor burden groups according to the up-to-7 criteria which is defined as the sum of the size of the largest tumor and the total number of tumors. The combination use of tyrosine kinase inhibitors (TKI) was documented and overall survival was analyzed.

Among the 129 patients receiving ICI, the median age was 63.2 years old, and 76.6% were male. Eighty-five patients (65.9%) were beyond up-to-7 criteria. Patients receiving ICI had median overall survival time of 15 months and had progression-free survival time of 6.2 months. In multivariate Cox regression analysis, the Child-Turcotte-Pugh (CTP) score B (adjusted HR: 3.103 (CI: 1.629-5.912), P = 0.0006), AFP decreased more than 10% from the baseline (adjusted HR: 0.463 (CI: 0.270-0.794), P = 0.0052), and out of up-to-7 criteria (adjusted HR:1.808 (CI:1.007-3.245), P = 0.0472) were the independent predictive factors for mortality. Among patients beyond up-to-7 criteria, 23.5% (n = 20) received combination treatment with TKI and ICI. Moreover, patients using combination treatment showed significantly better survival than those without combination treatment (1st year cumulative survival rate 61% vs 30%, log-rank P = 0.018).

Baseline CTP score, tumor burden, as well as AFP response during ICI treatment were the independent predictive factors for survival. Furthermore, among HCC patients beyond up-to-7 criteria, combination treatment was associated with improved survival than those without combination treatment.