RESUMEN
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.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Quinolinas , Carcinoma Hepatocelular/patología , Humanos , Indoles , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Receptor de Muerte Celular Programada 1 , Quinolinas/efectos adversos , Estudios RetrospectivosRESUMEN
Hypoxiainduciblefactor 1α (HIF1α) is a marker for poor prognosis in the majority of the cancer types, and it has been revealed to be essential for maintaining cancer stem cells (CSCs). In the present study, it was determined that the expression of HIF1α and CSCrelated genes under hypoxic conditions was upregulated. Stable knockdown of HIF1α significantly inhibited cell proliferation, migration and tumour growth in vivo in oesophageal squamous cell carcinoma (ESCC). A previous study revealed that the Wnt/ßcatenin pathway may play a key role in maintenance and progression of CSCs. Therefore, it was also revealed that stable knockdown of HIF1α reduced the formation of spheroid body cells, the expression of CSCrelated genes and Wnt/ßcatenin pathwayrelated target genes, as well as the activity of the Wnt/ßcatenin pathway. Collectively, the present results indicated that HIF1α may regulate the stemness of ESCC by activating the Wnt/ßcatenin pathway.