Adjuvant therapy with donafenib plus anti–PD-1 antibody for patients (pts) with hepatocellular carcinoma (HCC) at high risk of recurrence after resection (PATH study).

Abstract

e16228 Background: There is no universally accepted standard treatment option or strategy for post-surgery adjuvant therapy for HCC. Among BCLC A/B patients with MVI, adjuvant TACE provided a 1-year recurrence-free survival rate (RFSR) of around 60-70%. We conducted a pilot study to explore the utility of donafenib combined with anti-PD-1 antibody as adjuvant therapy for pts with high risks of recurrence. Methods: It was planned to enroll 30 HCC pts who had undergone radical surgery and with at least one of the following risk factors: a) Presence of microvascular invasion (MVI); b) Presence of satellite nodule(s); c) > 3 tumor nodules; d) Portal vein tumor thrombus. Pts with invasion of main portal venous were excluded. Donafenib plus anti-PD-1 antibody was initiated at 4 to 8 weeks after resection and continued for up to six months. No other adjuvant therapies were allowed before enrollment and during the study, except for anti-virus treatment. The primary endpoint was the cumulative 1-year RFSR. The secondary endpoints included recurrence-free survival (RFS), overall survival, and safety. Results: From June 2020 to November 2023, a total of 30 pts were recruited. 27 pts were included in efficacy analysis. The mean and median follow-up time was 347.9 days and 179.5 days. The mean and median time from surgery to enrollment was 42.5 days and 42.0 days. MVI was the most common risk factor (Table). Majority of the pts had only one risk factor. Relapse occurred in two pts (7.4%) and RFS was very immature. The RFSR at one year was 89.7% (90% CI, 70.6%-96.7%) in all the evaluable pts, and slightly higher in pts with M1 or only one risk factor (92.9% [90% CI, 68.1%-98.6%] and 93.3% [90% CI, 69.9%-98.7%], respectively). No deaths were observed. In 30 pts who had received at least one dose, the incidence of grade 3 treatment-related adverse events (TRAEs) was 40.0% (12/30). No grade 4 or 5 TRAEs were reported. The grade 3 TRAEs occurred in ≥2 pts were palmar-plantar erythrodysesthesia syndrome (13.3%), rash (13.3%), alanine aminotransferase increased (10.0%), and aspartate aminotransferase increased (6.7%). Conclusions: These results showed that a regimen of 6 months of adjuvant therapy with donafenib plus anti-PD-1 antibody may be efficient to reduce recurrence for BCLC A/B pts at high risk of recurrence, particularly those with ≤2 risk factors. No new safety issues were noticed. Clinical trial information: NCT04418401 . [Table: see text]