Updated results of the PATH study: Adjuvant therapy with donafenib plus a PD-1 inhibitor for patients with hepatocellular carcinoma at high risk of recurrence after resection.

571 Background: There is no universally accepted standard treatment option or strategy for post-surgery adjuvant therapy in hepatocellular carcinoma (HCC). Among BCLC A/B patients (pts) with MVI, adjuvant transarterial chemoembolization has been reported to provide a 1-year recurrence-free survival (RFS) rate of around 60-70%. We conducted a pilot study to explore the utility of donafenib combined with a PD-1 inhibitor as adjuvant therapy for pts at high risk of recurrence. Herein, we present the updated results with a median follow-up of 11.6 months. Methods: It was planned to enroll 30 HCC pts who had undergone radical surgery and presented with at least one of the following risk factors: a) Presence of microvascular invasion (MVI); b) Presence of satellite nodule(s); c) More than three tumor nodules; d) Portal vein tumor thrombus. Pts with invasion of the main portal venous system were excluded. Donafenib combined with a PD-1 inhibitor (i.e., toripalimab) was initiated at 4 to 8 weeks post-resection and was to be continued for up to six months, unless recurrence occurred or there was an intolerable adverse reaction. No other adjuvant therapies were permitted before enrollment and during the study, except for anti-virus treatment. The primary endpoint was the cumulative 1-year RFS rate. The secondary endpoints included overall survival, quality of life (QoL) measured with the FACT- Hepatobiliary questionnaire, and safety. Results: From June 2020 to November 2023, a total of 30 pts were recruited. 27 pts were included in the efficacy analysis. The median time from surgery to enrollment was 1.4 months. MVI was the most common risk factor (n=25, 92.6%). The majority of the pts had only one risk factor (n=23, 85.2%). As of the data cutoff on August 13, 2024, relapse had occurred in four pts and the median RFS was not reached. The 1-year RFS rate was 81.6% (90% CI, 67.8%-95.4%) in all evaluable pts. QoL showed a mild increase from baseline while on adjuvant therapy. No deaths were observed. In the 30 pts who had received at least one dose, the incidence of any grade and grade 3 treatment-related adverse events (TRAEs) were 90.0% (27/30) and 40.0% (12/30), respectively. No grade 4 or 5 TRAEs were reported. The grade 3 TRAEs occurring in at least two pts were palmar-plantar erythrodysesthesia syndrome (13.3%), rash (13.3%), increased alanine aminotransferase (10.0%), and increased aspartate aminotransferase (6.7%). Conclusions: The study's duration exceeded expectations due to slow recruitment. Nonetheless, it showed a promising outcome with a regimen of 6 months of adjuvant therapy with donafenib plus toripalimab in BCLC A/B pts at high risk of recurrence. An improvement in QoL was observed among patients during the adjuvant therapy. No new safety issues were identified. Clinical trial information: NCT04418401 .