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2022年广泛期小细胞肺癌(SCLC)最新进展

A 2022 Update on Extensive Stage Small-Cell Lung Cancer (SCLC).

作者信息

Oronsky Bryan, Abrouk Nacer, Caroen Scott, Lybeck Michelle, Guo Xiaoning, Wang Xiaohui, Yu Zhongwen, Reid Tony

机构信息

EpicentRx Inc., Department of Clinical Research, 11099 North Torrey Pines Road, Suite 160, La Jolla, CA 92037, USA.

Clinical Trials Innovations, Mountain View, CA, 94043, USA.

出版信息

J Cancer. 2022 Jul 18;13(9):2945-2953. doi: 10.7150/jca.75622. eCollection 2022.

Abstract

For close to 40 years small-cell lung cancer (SCLC) was adrift, as listless, and as idle as a painted ship on a painted ocean, with nary a breeze to blow in the direction of clinical progress or change. The preferred decades-old first line regimen was etoposide-platinum, to which ≥50% of patients respond, followed by decades-old, tired topotecan in second line for platinum sensitive patients, full stop, because there were no approved therapeutic options (nor generally any compelling experimental ones) in third line or beyond. In 2012 SCLC was designated by the U.S. Congress as a "recalcitrant" tumor type and for good reason: because most patients relapse, after the generally favorable response in first line, respond poorly, if at all to subsequent therapies, and rarely survive beyond 1 year. A significant sea change occurred in 2018 with the approval of nivolumab followed by pembrolizumab and atezolizumab in 2019, durvalumab in 2020, accelerated approval for lurbinectedin in 2020 and trilaciclib in 2021 for myelosuppression. In 2021, the US indications for nivolumab and pembrolizumab were withdrawn. Suddenly, a tumor type, whose name was virtually synonymous with stalled progress and movement, and which was much less well studied and funded than its more prevalent cousin, non-small cell lung cancer (NSCLC), finds itself in the eye of the storm, that is, at the epicenter of an intense flurry and ferment of activity, not all of it positive. This review surveys approved drugs and select up-and-coming ones in development for extensive stage SCLC.

摘要

近40年来,小细胞肺癌(SCLC)一直处于停滞状态,就像一艘画在海洋上的彩绘船一样无精打采、无所作为,没有一丝微风能推动临床进展或变革。几十年来一直首选的一线治疗方案是依托泊苷联合铂类药物,≥50%的患者对此有反应,随后对于铂类敏感的患者,二线治疗使用沿用数十年、已显疲态的拓扑替康,仅此而已,因为三线及以上没有获批的治疗选择(通常也没有任何引人注目的实验性选择)。2012年,美国国会将SCLC指定为“难治性”肿瘤类型,这是有充分理由的:因为大多数患者在一线治疗取得普遍良好反应后会复发,对后续治疗反应不佳,甚至根本没有反应,很少能存活超过1年。2018年发生了重大变化,纳武单抗获批,随后2019年帕博利珠单抗和阿特珠单抗获批,2020年度伐利尤单抗获批,2020年鲁比卡丁因骨髓抑制获得加速批准,2021年曲拉西利获批。2021年,纳武单抗和帕博利珠单抗在美国的适应证被撤回。突然间,一种肿瘤类型,其名字几乎成了进展停滞和缺乏进展的代名词,而且与更常见的非小细胞肺癌(NSCLC)相比,其研究和资金投入要少得多,却发现自己处于风暴的中心,也就是激烈活动的核心,并非所有这些活动都是积极的。本综述调查了已获批的药物以及正在研发中的、用于广泛期SCLC的一些有潜力的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3304/9330463/642a72fd26d0/jcav13p2945g001.jpg

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