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免疫检查点抑制剂在小细胞肺癌中的应用:部分实现的潜力。

Immune Checkpoint Inhibitors in Small Cell Lung Cancer: A Partially Realized Potential.

机构信息

Department of Medicine, Georgetown University, Washington, DC, USA.

出版信息

Adv Ther. 2019 Aug;36(8):1826-1832. doi: 10.1007/s12325-019-01008-2. Epub 2019 Jun 17.

Abstract

Small cell lung cancer (SCLC) is a highly lethal subtype of lung cancer that has seen few therapeutic advances, despite ongoing concerted efforts. Immunotherapy has been an effective option in other carcinogen-related cancers and has shown modest activity in SCLC. Monotherapy with the anti-PD-1 antibody nivolumab in patients with at least two prior lines of therapy was associated with a response rate of 11.9% and a median duration of response of 17.9 months, leading to accelerated approval by the Food and Drug Administration (FDA) as third-line therapy for SCLC. Second-line checkpoint inhibitors have not performed well enough to change the standard of care, and maintenance immunotherapy has not shown significant benefit. However, the incorporation of concurrent immunotherapy in the first-line treatment of SCLC has improved outcomes. The addition of the anti-PD-L1 antibody atezolizumab to standard carboplatin plus etoposide led to an improvement in progression free survival (PFS) and overall survival, the first such improvement in over 30 years leading to the approval of atezolizumab as part of first-line therapy for advanced SCLC. While these landmark approvals offer promising novel treatment options for this recalcitrant disease, more work is needed to optimize their delivery and to build upon these important advances.

摘要

小细胞肺癌(SCLC)是一种高度致命的肺癌亚型,尽管人们一直在不懈努力,但几乎没有取得任何治疗进展。免疫疗法在其他与致癌物相关的癌症中是一种有效的选择,并且在 SCLC 中显示出适度的活性。抗 PD-1 抗体 nivolumab 在至少接受过两线治疗的患者中的单药治疗与 11.9%的缓解率和 17.9 个月的中位缓解持续时间相关,这导致食品和药物管理局 (FDA) 加速批准其作为 SCLC 的三线治疗药物。二线检查点抑制剂的表现不够好,无法改变标准治疗方法,而维持性免疫疗法也没有显示出显著的益处。然而,将同步免疫疗法纳入 SCLC 的一线治疗已改善了结果。将抗 PD-L1 抗体 atezolizumab 加入标准卡铂加依托泊苷中可改善无进展生存期(PFS)和总生存期,这是 30 多年来的首次此类改善,导致 atezolizumab 被批准作为晚期 SCLC 的一线治疗药物。虽然这些里程碑式的批准为这种难治性疾病提供了有前途的新治疗选择,但仍需要做更多的工作来优化它们的应用,并在此基础上取得重要进展。

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