Postoperative adjuvant donafenib combined with PD-1 checkpoint inhibitor for patients at high risk of recurrence.

Abstract

e16276 Background: There is currently no internationally standardized adjuvant therapy for HCC patients with high-risk recurrence and metastasis after surgery, and the high risk of postoperative recurrence remains an unresolved issue. Therefore, the purpose of this study is to explore the efficacy and safety of Donafenib combined with PD-1 checkpoint inhibitor in the high recurrence population after HCC radical surgery. Methods: We retrospectively collected information on high-risk of recurrence HCC patients who underwent radical surgery at Shandong Provincial Hospital between October 2021 and August 2024 and received adjuvant therapy with Donafenib+PD-1 checkpoint inhibitor. High-risk of recurrence is defined as having any of the following risk factors: a) Multiple tumors or diameter > 5cm; b) Presence of satellite nodule(s); c) Carcinoma embolus; d) AFP remains abnormal; e) Edmondson stage III-IV. Patients included in this study must meet the following criteria: 1.Confirmed HCC by postoperative pathological examination; 2. No other anti-tumor treatment except antiviral therapy, Donafenib, and PD-1 checkpoint inhibitor; 3. Complete follow-up information. The main research outcomes include the short-term survival prognosis and the incidence of adverse events. The 1-year recurrence-free survival (RFS) rate refers to the cumulative percentage of patients who did not experience recurrence or died within 1 year after achieving a radical state. Adverse events (AE) are assessed according to the CTCAE 5.0. Results: A total of 28 patients were enrolled in this study, the population was predominantly male (96.4%), and the median age was 60 years (IQR: 57-66 years). 21.4% of patients had preoperative AFP > 400ng/ml, 46.4% had a tumor diameter > 5cm. Most patients had a single tumor (71.4%), 32.1% had Edmondson–Steiner grade III-IV, and 57.1% had two or more high-risk factors simultaneously. At a median follow-up of 13.9 months, 4 patients experienced recurrence or death. The median RFS was 29.9 months, the 1-year RFS rate was 94.4%, and the 18-month RFS rate was 61.6%. The median overall survival (OS) was not reached. Subgroup analysis showed that patients with a tumor diameter ≥ 5cm had a lower RFS rate than those with a tumor diameter < 5cm (12-month RFS rate: 90% vs 100%; 18-month RFS rate: 50.0% vs 66.7%). The incidence of any adverse reaction was 89.3%, with common adverse reactions including rash, hand-foot skin reaction, and diarrhea. Eight patients (28.6%) had grade 3 adverse events, of which 7 continued to take medication after symptomatic treatment, and 1 terminated treatment. There were no grade 4 or 5 TRAE. Conclusions: Postoperative adjuvant therapy with Donafenib combined with PD-1 checkpoint inhibitor effectively reduces early recurrence in HCC patients at high risk of recurrence, while demonstrating good safety and tolerability.