Abstract
Background: Unresectable hepatocellular carcinoma (uHCC) patients with Child-Pugh grade B have limited treatment options and poor outcomes.
Methods: Patients with uHCC and Child-pugh B who received lenvatinib plus PD-1 inhibitors or sorafenib plus PD-1 inhibitors at one of three centers were retrospectively reviewed. These patients were divided into two subgroups: one with Child-pugh B7 (Group A, n =106) and another with Child-pugh B/9 (Group B, n = 73). Overall survival (OS) was defined as the primary endpoint. Secondary endpoints included time to progression (TTP), the objective response rate (ORR), and safety. Prognostic factors were evaluated using multivariate Cox proportional hazards models, while nomograms were constructed to predict 12-month survival.
Results: Between December 31, 2020 and March 30, 2023, a total of 179 patients were enrolled. The objective response and disease control rates of patients in the Child–pugh groups B and A were 26.0% and 76.7%, and 33.0% and 83.0%, respectively. There was no difference in median TTP (6.3 vs. 7.8 months, P = 0.28) or OS (14.0 vs. 17.8months, P = 0.20) between Group B and Group A. However, while the safety profiles were comparable between the two groups, patients with Child-pugh B8/9 had a significantly higher frequency of dose reductions and discontinuations (P = 0.04 and P < 0.001), compared to those with Child-pugh B7. According to the results of multivariate analysis，we constructed a nomogram to predict 12-month survival rates，considering tumor size, BCLC stage, tumor response , drug resistance. The nomogram-related receiver operating characteristics (ROC) curves indicated that the area under the curve (AUC) values were 0.752. Furthermore, the calibration curves revealed good agreement between real measurements and nomogram predictions.
Conclusions:
A combination of multi-kinase inhibitors (lenvatinib or sorafenib) plus PD-1 inhibitors was safe, well-tolerated, and especially it can also benefit patients with uHCC and Child-pugh B8/9.