Lenvatinib,a multi-kinase inhibitor,has been approved asfirst-line treatment for advanced hepatocellular carcinoma(HCC),but its efficacy is limited.We have shown previously that lenvatinib and epidermal growth factor ...Lenvatinib,a multi-kinase inhibitor,has been approved asfirst-line treatment for advanced hepatocellular carcinoma(HCC),but its efficacy is limited.We have shown previously that lenvatinib and epidermal growth factor receptor tyrosine kinase inhibitor(EGFRTKI)combination therapy overcomes lenvatinib resistance in HCC with high level of EGFR expression(EGFR^(high)).We present here the results of a single-arm,open-label,exploratory study of lenvatinib plus the EGFR-TKI gefitinib for patients with HCC resistance to lenvatinib(NCT04642547;n=30).Only patients with EGFR^(high) HCC and progressive disease after lenvatinib treatment were recruited in the study.The most frequent adverse events of all grades were fatigue(27 patients;90%),followed by rash(25 patients;83.3%),diarrhea(24 patients;80%),and anorexia(12 patients;40%).Among 30 patients,9(30%)achieved a confirmed partial response and 14(46.7%)had stable disease according to mRECIST criteria.Based on RECIST1.1,5(16.7%)achieved a confirmed partial response and 18(60%)had stable disease.The estimated median progression free survival(PFS)and overall survival(OS)time were 4.4 months(95%CI:2.5 to 5.9)and13.7 months(95%CI:9.0 to NA),respectively.The objective response rate(ORR)of the patients in the present study compares very favorable to that seen for the two approved second line treatments for HCC(cabozantinib ORR of 4%;regorafenib ORR of 11%).Given that this combination was well-tolerated,a further clinical study of this combination is warranted.展开更多
Dear Editor,Available evidence regarding the most suitable treatment strategies for hepatocellular carcinoma(HCC)with inferior vena cava tumor thrombus(IVCTT)is extremely limited,and the median overall survival time f...Dear Editor,Available evidence regarding the most suitable treatment strategies for hepatocellular carcinoma(HCC)with inferior vena cava tumor thrombus(IVCTT)is extremely limited,and the median overall survival time for these patients after liver resection is only 17.76 months[1].Other local or systemic treatments for HCC with IVCTT result in a median overall survival time ranging from 5.88 to 15.36 months[1–3].Thus,new therapeutic strategies are urgently needed to improve the survival of HCC patients with IVCTT.Chimeric antigen receptor(CAR)T-cell therapy has seen success in treating B-cell neoplasms with impressive outcomes[4].However,this therapy alone has shown limited efficacy on solid tumors,such as HCC[5].展开更多
Local ablation technologies, such as radiofrequency ablation (RFA), microwave ablation (MWA) andcryoablation, have become a standard treatment option for hepatocellular carcinoma (HCC) less than5 cm in size, particula...Local ablation technologies, such as radiofrequency ablation (RFA), microwave ablation (MWA) andcryoablation, have become a standard treatment option for hepatocellular carcinoma (HCC) less than5 cm in size, particularly in individuals who are not candidates for hepatectomy. Except for equivalentprognosis and efficiency, RFA has various advantages over surgical excision, including a lower rate ofcomplications, a cheaper cost, more normal tissue preservation, and a shorter hospital stay. However, therate of tumor recurrence and/or distant metastasis after RFA therapy is still high. RFA has been widelyemployed in multiple cancers, large cancer, and lesion identified at “high-risk” sites in recent years, withthe advancement of ablation types and operating techniques, particularly the combined use of manytechnologies. The real value of RFA technology has been more fully reflected.We will examine the status,progress, and problems of RFA in the treatment of HCC in this review.展开更多
基金supported by the National Natural Science Foundation(Nos.82222047,82073039,82330095,81502672,and 82070619)the Program of Shanghai Academic/Technology Research Leader(No.22XD1423100)+2 种基金the National Key Research and Development Program of China(2022YFC2804300)Shanghai Municipal Commission of Health and Family Planning(2022XD057)the Shanghai Committee of Science and Technology(23ZR1439000 and 22S11900500).
文摘Lenvatinib,a multi-kinase inhibitor,has been approved asfirst-line treatment for advanced hepatocellular carcinoma(HCC),but its efficacy is limited.We have shown previously that lenvatinib and epidermal growth factor receptor tyrosine kinase inhibitor(EGFRTKI)combination therapy overcomes lenvatinib resistance in HCC with high level of EGFR expression(EGFR^(high)).We present here the results of a single-arm,open-label,exploratory study of lenvatinib plus the EGFR-TKI gefitinib for patients with HCC resistance to lenvatinib(NCT04642547;n=30).Only patients with EGFR^(high) HCC and progressive disease after lenvatinib treatment were recruited in the study.The most frequent adverse events of all grades were fatigue(27 patients;90%),followed by rash(25 patients;83.3%),diarrhea(24 patients;80%),and anorexia(12 patients;40%).Among 30 patients,9(30%)achieved a confirmed partial response and 14(46.7%)had stable disease according to mRECIST criteria.Based on RECIST1.1,5(16.7%)achieved a confirmed partial response and 18(60%)had stable disease.The estimated median progression free survival(PFS)and overall survival(OS)time were 4.4 months(95%CI:2.5 to 5.9)and13.7 months(95%CI:9.0 to NA),respectively.The objective response rate(ORR)of the patients in the present study compares very favorable to that seen for the two approved second line treatments for HCC(cabozantinib ORR of 4%;regorafenib ORR of 11%).Given that this combination was well-tolerated,a further clinical study of this combination is warranted.
基金This clinical study(NCT02395250)was supported by the Research Fund of the State Key Laboratory of Oncogenes and Related Genes(91-15-04)the Program of Shanghai Subject Chief Scientist(No.16XD1402600)+3 种基金the National Natural Science Foundation(Nos.81502672,82222047,82073039,and 82070619)the Program of Shanghai Academic/Technology Research Leader(No.22XD1423100)the Shanghai Science and Technology Innovation Action Plan(No.16DZ1910700)Shanghai Science and Technology Commission Grant(No.23ZR1439000).
文摘Dear Editor,Available evidence regarding the most suitable treatment strategies for hepatocellular carcinoma(HCC)with inferior vena cava tumor thrombus(IVCTT)is extremely limited,and the median overall survival time for these patients after liver resection is only 17.76 months[1].Other local or systemic treatments for HCC with IVCTT result in a median overall survival time ranging from 5.88 to 15.36 months[1–3].Thus,new therapeutic strategies are urgently needed to improve the survival of HCC patients with IVCTT.Chimeric antigen receptor(CAR)T-cell therapy has seen success in treating B-cell neoplasms with impressive outcomes[4].However,this therapy alone has shown limited efficacy on solid tumors,such as HCC[5].
基金This work was supported by the National Key R&D Program of China(2020YFC0122300)the General programs of the National Natural Science Foundation of China(82070619)to B.Zhai。
文摘Local ablation technologies, such as radiofrequency ablation (RFA), microwave ablation (MWA) andcryoablation, have become a standard treatment option for hepatocellular carcinoma (HCC) less than5 cm in size, particularly in individuals who are not candidates for hepatectomy. Except for equivalentprognosis and efficiency, RFA has various advantages over surgical excision, including a lower rate ofcomplications, a cheaper cost, more normal tissue preservation, and a shorter hospital stay. However, therate of tumor recurrence and/or distant metastasis after RFA therapy is still high. RFA has been widelyemployed in multiple cancers, large cancer, and lesion identified at “high-risk” sites in recent years, withthe advancement of ablation types and operating techniques, particularly the combined use of manytechnologies. The real value of RFA technology has been more fully reflected.We will examine the status,progress, and problems of RFA in the treatment of HCC in this review.
