Abstract 935P
Background
An open-label, randomized, multicentre phase II/III trial (ZGDH3) has demonstrated that compared with sorafenib, donafenib significantly prolonged the overall survival (OS) of patients with advanced hepatocellular carcinoma (HCC). It also showed a better survival benefit than sorafenib in the prespecified subgroup analysis. This article aimed to further explore whether the baseline characteristics of patients other than the predefined subgroups were related to the better OS benefit of donafenib.
Methods
This analysis was based on the ITT population of ZGDH3 study. The median OS of donafenib and sorafenib was assessed by the Kaplan-Meier method and was compared for each baseline characteristic subgroup. The stratified Cox proportional hazard model was used to calculate the hazard ratio and its 95% confidence interval.
Results
668 patients were included in the analysis (334 in each group). Donafenib was associated with a trend of improved OS benefit when compared with sorafenib in most subgroups (HR < 1), with significant differences in the following subgroups: ECOG PS score of 1 (p = 0.0462), normal AST (p = 0.0439), no prior interventional therapy (p = 0.0433), lung target lesion absent (p = 0.0062), lymph node target lesion present (p = 0.0277), age ≥ 65 years (p = 0.0089), and BMI < 25 (p = 0.0054). Among patients ≥ 65 years of age, the median OS of the donafenib group and the sorafenib group was 12.1 and 8.9 months, respectively, representing the most significant benefit in the donafenib group (HR 0.516, 95% CI 0.315–0.847). Table: 935P
Exploratory subgroup comparison of donafenib vs sorafenib in OS
| Subgroup | Median (months) | HR (95% CI) |
| ECOG PS 1 | 11.7 vs 9.6 | 0.804 (0.649, 0.996) |
| AST Normal | 15.7 vs 13.5 | 0.776 (0.606, 0.993) |
| No prior interventional therapy | 11.5 vs 8.8 | 0.741 (0.554, 0.991) |
| Lung target lesion absent | 13.0 vs 10.1 | 0.758 (0.622, 0.925) |
| Lymph node target lesion present | 7.9 vs 7.2 | 0.599 (0.380, 0.945) |
| Age ≥ 65 | 12.1 vs 8.9 | 0.516 (0.315, 0.847) |
| BMI <25 | 11.2 vs 9.1 | 0.757 (0.622, 0.921) |
Conclusions
Donafenib exhibited a better survival benefit than sorafenib in most of the baseline characteristic subgroups, which further confirmed the excellent efficacy of donafenib in the first-line treatment of advanced HCC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Zelgen.
Disclosure
All authors have declared no conflicts of interest.