Donafenib plus TACE with or without PD-(L)1 inhibitors for the treatment of unresectable hepatocellular carcinoma: A multi-center retrospective study.

Abstract

e16183 Background: Donafenib, a multikinase inhibitor, have shown superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC. PD-(L)1 inhibitors also have shown efficacy and tolerability in patients with HCC, and adding this combination to TACE may enhance clinical benefit and may increase the hepatotoxicity at the same time. Thus, this real-world study has been conducted on TACE combined with donafenib with or without immune checkpoint inhibitors to evaluate the efficacy and hepatotoxicity simultaneously. Methods: In this retrospective, multicenter study, adults aged 18 years or older with unresectable hepatocellular carcinoma were screened who received donafeib and TACE with or without PD-(L)1 inhibitors at the Affiliated hospital of Qingdao University and Shandong Cancer Hospital in China from September 2021 to October 2024. Results: 76 patients were screened including 50 who received donafenib and TACE plus PD-1 inhibitors and 26 who received donafenib and TACE. Mean age was 62.6 years, 64 (84.2%) of 76 participants were male. As of data cutoff (Dec 25, 2024), median duration of follow-up was 10.3 months. According to mRECIST, the ORR and DCR were 67.1% (51/76) and 94.7% (72/76), respectively. The median progression-free survival was 11.2months (95% CI 9.2–NA). The median overall survival was not reached (95% CI NA–NA), while the 12-month survival rate was 83.4%, and the 24 month survival rate was 77.0%. In subgroup analyses, a superior survival benefit and a higher ORR were achieved in patients without vascular invasion than those with vascular invasion (mPFS: 12.6m vs 5.9m, p = 0.0024; mOS: NA vs NA, p = 0.046; ORR: 76.6% vs 51.7%, p = 0.047). The mean albumin-bilirubin scores did not deteriorate after treatment, compared with the scores at the baseline and 65 patients (85.5%) maintained or improved ALBI grading at the end of treatment. Any grade of study treatment-related adverse events occurred in 50 participants. The most common adverse events were rash and Hand-foot skin reactions. Conclusions: Donafenib combined with TACE plus PD-(L)1 inhibitors is a promising therapeutic regimen in unresectable hepatocellular carcinoma. Donafenib may be the first choice of combination therapy because it can prevent liver function deterioration and achieve a high objective response rate.