Updated results from ALTER-H004 trial: Anlotinib combined with TACE as adjuvant therapy for patients with hepatocellular carcinoma at high risk of recurrence after surgery—A single arm, multi-center, phase II clinical trial.

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e16222 Background: Hepatectomy is deemed as a curative treatment for patients (pts) with hepatocellular carcinoma (HCC). Unfortunately, high recurrent risk after curative resection compromised the long-term survival of HCC significantly. Transarterial chemoembolization (TACE) as adjuvant therapy was proved to improve therapeutic outcomes for pts with high recurrent risk after hepatectomy. However, the survival benefit of TACE remained unsatisfactory. ALTER-H004 trial was designed to identify the efficacy and safety of anlotinib as maintenance adjuvant treatment following TACE in pts with HCC. The preliminary results of ALTER-H004 had been reported at 2022 ASCO (e16120). Here we reported the results at the data cutoff of January 15, 2023. Methods: Pts with one of the following high risk factors after hepatectomy were eligible: ≥5cm and <10cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus (Cheng's classification I/II). Eligible pts received conventional TACE treatment within 1-2 months after hepatectomy, and on the 4th day after TACE treatment, oral anlotinib (12mg, qd, 2 weeks on 1 week off) was given until disease recurrence or unacceptable toxicity. The predefined sample size was 30. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: At January 15, 2023, 29 pts were enrolled and 28 pts were available for prognostic assessment, among whom, 11 pts were still on treatment and 9 relapsed, 3 withdrew the consent, 5 discontinued own to intolerable adverse reactions. The longest duration of treatment is 27.83 months. The median DFS has not reached yet and the 1-year DFS rate was 76.46% (95% CI: 54.83~88.70) and 2-year DFS rate was 65.41% (95% CI: 41.70~81.39). Safety profile indicated that 18 pts (64.3%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs were detected in 5 pts (17.9%) including hypertension (7.1%), leukocytopenia (7.1%) and ascites (3.6%). No grade 4 or 5 TRAEs were observed. Conclusions: Anlotinib combined with TACE as adjuvant therapy in pts with HCC at high recurrent risk exhibited promising prognosis and tolerable safety profile preliminarily, and the conclusion needed to be confirmed in large-scale clinical trials subsequently. Clinical trial information: NCT04213118 .