Effectiveness and Safety of Anlotinib with or without PD-1 Blockades in the Treatment of Patients with Advanced Primary Hepatocellular Carcinoma: A Retrospective, Real-World Study in China

Abstract

Purpose Anlotinib, a novel multi-target tyrosine kinase inhibitor, has shown encouraging antitumor effects in advanced hepatocellular carcinoma (HCC). This study evaluated the effectiveness and safety of anlotinib with or without programmed death-1 (PD-1) blockades for patients with advanced primary HCC in a real-world setting in China. Patients and Methods Between July 2019 and May 2021, 27 patients with advanced primary HCC who received at least 2 cycles of anlotinib were included in this retrospective study. Primary endpoint was objective response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results Of the 27 patients, ORR and DCR were 25.93% and 74.07%, respectively. The median follow-up time was 6.27 months (range: 1.30–17.40) with a median PFS and OS of 3.29 months (95% CI: 1.31–15.47) and 6.21 months (95% CI: 2.23–15.87), respectively. A total of 14 patients received anlotinib and PD-1 blockade combination therapy, and 13 received anlotinib monotherapy. No significant differences were observed in ORR (28.57 vs 23.08%), DCR (71.43 vs 76.92%), PFS (3.38 [95% CI: 2.66–13.14] vs 11.86 months [95% CI: 4.27–15.93]) and OS (4.90 [95% CI: 2.56–13.60] vs 11.04 months [95% CI: 1.31–17.18]) between the two groups (all p >0.05). Treatment-related AEs were reported in 88.89% of patients. Grade 3 AE was bleeding, which occurred in 3 patients (11.11%). Conclusion Anlotinib yielded a promising efficacy and manageable safety in patients with advanced primary HCC irrespective of whether patients received PD-1 blockades, indicating that anlotinib might be a promising treatment option for this patient population.

Aurora-A inhibitor synergistically enhances the inhibitory effect of anlotinib on hepatocellular carcinoma

“…When HCC is expected to become a new approved indication for anlotinib, taking into account the possible future drug resistance in advance, combination therapy is an effective way to improve the e cacy of anlotinib in the future. As mentioned earlier, the combination of anlotinib with immunotherapy has also been shown to be safe in clinical trials and provides promising clinical bene ts in patients with unresectable or metastatic HCC who have not received systemic therapy 7,11 . As an anti-angiogenic drug, anlotinib inhibits tumor angiogenesis to achieve the purpose of anti-tumor.…”

Anlotinib plus Sintilimab achieved in an antitumor effect of complete remission in a patient with advanced hepatocellular carcinoma: a case report

“…In patients with advanced non-small-cell lung cancer, many clinical studies demonstrated that anti-PD-1 treatment concomitant with anlotinib has favorable antitumor activities as the first-line or posteriorline therapeutic options [10][11][12][13]. In patients with advanced HCC, anlotinib alone could yield a promising efficacy irrespective of whether patients received PD-1 blockades [14]. Two clinical trials reported that when combined with PD-1 blockades, anlotinib showed more robust antitumor activities with an objective response rate of over 30% as the first-line treatment of advanced HCC [6,15].…”

Effectiveness and safety of anlotinib with or without S-1 in the treatment of patients with advanced hepatocellular carcinoma in a Chinese population: a prospective, phase 2 study

“…( 5) There was no hypertension. (6) The patient signed the informed consent form. The main exclusion criteria were as follows:…”

“…Studies have shown that anlotinib (ANL) is effective and well tolerated as a treatment for patients with advanced HCC. 5,6 The results showed that fluorouracil was effective for HCC. [7][8][9] Both S1 and capecitabine are fluorouracils.…”