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T-VEC联合依匹木单抗治疗晚期恶性黑色素瘤的多中心随机Ⅱ期临床试验的5年随访结果解读 被引量:1
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作者 纪青 莫淼 《肿瘤学杂志》 CAS 2023年第7期626-634,共9页
溶瘤病毒联合免疫检查点抑制剂方案一直是恶性黑色素瘤治疗的研究热点。一项多中心、开放标签的随机Ⅰb/Ⅱ期临床试验(NCT01740297)对比了溶瘤病毒talimogene laherparepvec(T-VEC)联合依匹木单抗对比依匹木单抗单药在不可切除的ⅢB~Ⅳ... 溶瘤病毒联合免疫检查点抑制剂方案一直是恶性黑色素瘤治疗的研究热点。一项多中心、开放标签的随机Ⅰb/Ⅱ期临床试验(NCT01740297)对比了溶瘤病毒talimogene laherparepvec(T-VEC)联合依匹木单抗对比依匹木单抗单药在不可切除的ⅢB~ⅣM1c期恶性黑色素瘤患者中的疗效和安全性。该研究的Ⅱ期于2013年8月至2021年3月在美国、法国和德国的33个中心进行,筛选入组198例患者,以1∶1的比例随机接受T-VEC联合依匹木单抗或依匹木单抗单药治疗。主要研究终点是根据免疫相关应答标准评估的客观缓解率(objective response rate,ORR),关键次要终点包括持久反应率(durable response rate,DRR)、反应持续时间(duration of response,DOR)、无进展生存期(progression-free survival,PFS)、总生存期(overall survival,OS)和安全性。与依匹木单抗单药相比,联合用药组显著性改善了患者的ORR(35.7%vs 16.0%;OR=2.9,95%CI:1.5~5.7,P=0.003)。两组的DRR分别为33.7%和13.0%(P=0.001)。在达到客观缓解的患者中,联合用药组的中位DOR为69.2个月(95%CI:38.5~NA),单药组尚未达到。联合用药组的中位PFS为13.5个月,单药组为6.4个月(HR=0.78,95%CI:0.55~1.09,P=0.14)。联合用药组的5年OS率为54.7%,单药组为48.4%。5年随访中未发现新的安全性事件。这是首个达到主要研究终点的溶瘤病毒联合免疫检查点抑制剂的随机对照研究。5年随访数据提示T-VEC联合依匹木单抗能安全有效地改善晚期恶性黑色素瘤患者的治疗有效率,但从长期生存角度,联合用药并未给患者带来具有统计学差异的生存获益。 展开更多
关键词 溶瘤病毒 T-VEC 黑色素瘤 免疫检查点抑制剂
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Emerging systemic delivery strategies of oncolytic viruses:A key step toward cancer immunotherapy 被引量:5
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作者 Weiyue Ban Jianhuan Guan +4 位作者 Hanwei Huang Zhonggui He Mengchi Sun Funan Liu Jin Sun 《Nano Research》 SCIE EI CSCD 2022年第5期4137-4153,共17页
Oncolytic virotherapy(OVT)is a novel type of immunotherapy that induces anti-tumor responses through selective self-replication within cancer cells and oncolytic virus(OV)-mediated immunostimulation.Notably,talimogene... Oncolytic virotherapy(OVT)is a novel type of immunotherapy that induces anti-tumor responses through selective self-replication within cancer cells and oncolytic virus(OV)-mediated immunostimulation.Notably,talimogene laherparepvec(T-Vec)developed by the Amgen company in 2015,is the first FDA-approved OV product to be administered via intratumoral injection and has been the most successful OVT treatment.However,the systemic administration of OVs still faces huge challenges,including in vivo pre-existing neutralizing antibodies and poor targeting delivery efficacy.Recently,state-of-the-art progress has been made in the development of systemic delivery of OVs,which demonstrates a promising step toward broadening the scope of cancer immunotherapy and improving the clinical efficacy of OV delivery.Herein,this review describes the general characteristics of OVs,focusing on the action mechanisms of OVs as well as the advantages and disadvantages of OVT.The emerging multiple systemic administration approaches of OVs are summarized in the past five years.In addition,the combination treatments between OVT and traditional therapies(chemotherapy,thermotherapy,immunotherapy,and radiotherapy,etc.)are highlighted.Last but not least,the future prospects and challenges of OVT are also discussed,with the aim of facilitating medical researchers to extensively apply the OVT in the cancer therapy. 展开更多
关键词 oncolytic virotherapy oncolytic viruses talimogene laherparepvec systemic administration combination treatments
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