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作者信息

Basset-Seguin N

机构信息

Université Paris-7, service de dermatologie, hôpital Saint-Louis, Paris, France.

出版信息

Ann Dermatol Venereol. 2018 Nov;145 Suppl 5:VS36-VS41. doi: 10.1016/S0151-9638(18)31257-2.

DOI:10.1016/S0151-9638(18)31257-2
PMID:30477683
Abstract

Until recently, advanced BCC were only accessible to a highly morbid surgery not necessarily proving to be carcinologic, and leaving terrible dysmorphic sequelae hard to accept by the patient. Another possibility, the only one in case of metastatic BCC, was chemotherapy which efficacy has never been proven in a clinical trial. Radiotherapy is most often not accessible because of previous radiotherapy or because of the localization or the extension of the lesion. The discovery of the importance of the sonic hedgehog pathway in the physiopathology of BCC has opened a new strategy with the development of targeted anti SMO drugs inactivating the pathway. Two molecules have become available following Phase I and II studies: vismodegib (Erivedge®) the first in class indicated for locally advanced and metastatic BCC and sonidegib (Odomzo®) indicated only for locally advanced BCC. The pharmacokinetic profiles of sonidegib and vismodegib showed several differences. No head to head comparative studies are available between these two drugs. Their pivotal phase II studies had similar study designs and endpoints. The objective response rate (ORR) by central review for vismodegib was 47.6% (95% CI 35.5-60.6) at 21 months follow-up. The ORR for sonidegib according to central review at 18 months follow-up is 56.1% (95% CI 43.3-68.3). Although both treatments share a similar adverse event profile with possible numerically differences in incidence, most patients will discontinue hedgehog inhibitors treatment in the long term because of side effects. Some resistant cases to these drugs have been described but are rather rare. In case of resistance or bad tolerability to the drug future hopes rely on immunotherapy currently under investigation. © 2018. Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Prise en charge des carcinomes basocellulaires difficiles à traiter réalisé avec le soutien institutionnel de Sun Pharma.

摘要

直到最近,晚期基底细胞癌(BCC)的治疗只能通过一种高致残性手术来实现,这种手术不一定能保证肿瘤学上的疗效,而且会留下令患者难以接受的严重畸形后遗症。另一种可能性,也是转移性基底细胞癌唯一的治疗方法,是化疗,但化疗的疗效从未在临床试验中得到证实。由于先前接受过放疗、病变部位或范围等原因,放疗往往无法实施。随着在基底细胞癌生理病理学中发现音猬因子(sonic hedgehog)信号通路的重要性,人们开发了使该信号通路失活的靶向抗平滑肌瘤(SMO)药物,从而开启了一种新的治疗策略。经过I期和II期研究,已有两种药物可供使用:维莫德吉(Erivedge®),是首个被批准用于局部晚期和转移性基底细胞癌的同类药物;索尼德吉(Odomzo®),仅用于局部晚期基底细胞癌。索尼德吉和维莫德吉的药代动力学特征存在一些差异。目前尚无这两种药物的直接对比研究。它们的关键II期研究具有相似的研究设计和终点。在21个月的随访中,维莫德吉经中心评估的客观缓解率(ORR)为47.6%(95%置信区间35.5 - 60.6)。索尼德吉在18个月随访时经中心评估的ORR为56.1%(95%置信区间43.3 - 68.3)。尽管两种治疗的不良事件谱相似,只是在发生率上可能存在数值差异,但大多数患者最终会因副作用而停止使用刺猬因子抑制剂治疗。已经报道了一些对这些药物耐药的病例,但相当罕见。对于耐药或耐受性差的患者,未来的希望寄托在目前正在研究的免疫疗法上。© 2018. 由Elsevier Masson SAS出版。保留所有权利。本文是在太阳制药公司的机构支持下完成的关于难治性基底细胞癌治疗的增刊的一部分。

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