Department of Medical Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Montefiore Medical Center, Bronx, NY, 10461, USA.
Lung. 2021 Dec;199(6):579-587. doi: 10.1007/s00408-021-00486-y. Epub 2021 Nov 10.
Accounting for 14% of lung cancer, small cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy with rapid proliferation, early spread, and poor survival.
We provide an overview of recent advances regarding SCLC pathogenesis, subtypes, and treatment development through literature review of key trials.
There are no validated biomarkers or approved targeted treatments for this overly heterogeneous disease, but recent analyses have identified some promising targets and four major subtypes which may carry unique therapeutic vulnerabilities in SCLC. Treatment wise, only a third of patients present with limited stage SCLC, which can be managed with a combined modality approach with curative intent (usually chemo-radiotherapy, but in some eligible patients, surgery followed by systemic treatment). For advanced or extensive stage SCLC, combined chemotherapy (platinum-etoposide) and immunotherapy (atezolizumab or durvalumab during and after chemotherapy) has become the new standard front-line treatment, with modest improvement in overall survival. In the second-line setting, for disease relapse ≤ 6 months, topotecan, lurbinectedin, and clinical trials are reasonable treatment options; for disease relapse > 6 months, original regimen, topotecan or lurbinectedin can be considered. Moreover, Trilaciclib, a CD4/CD6 inhibitor, was recently FDA-approved to decrease the incidence of chemotherapy-related myelosuppression in SCLC patients.
While modest improvements in survival have been made especially in the metastatic setting with chemo-immunotherapy, further research in understanding the biology of SCLC is warranted to develop biomarker-driven therapeutic strategies and combinational approaches for this aggressive disease.
小细胞肺癌（SCLC）占肺癌的 14%，是一种具有高度侵袭性的神经内分泌恶性肿瘤，其特点为增殖迅速、早期扩散和生存预后差。
我们通过对关键试验的文献回顾，提供了关于 SCLC 发病机制、亚型和治疗进展的最新研究进展概述。
目前针对这种高度异质性疾病，尚无经过验证的生物标志物或获批的靶向治疗方法，但最近的分析已经确定了一些有前途的靶点和四个主要亚型，这些亚型在 SCLC 中可能具有独特的治疗弱点。在治疗方面，只有三分之一的患者表现为局限期 SCLC，可以采用联合治疗方法进行治疗（通常是化疗和放疗，但在一些符合条件的患者中，手术联合系统治疗）。对于广泛期或晚期 SCLC，联合化疗（铂类联合依托泊苷）和免疫治疗（化疗期间和之后联合阿替利珠单抗或度伐利尤单抗）已成为新的标准一线治疗方法，总生存期略有改善。在二线治疗中，对于疾病复发时间≤6 个月的患者，拓扑替康、鲁比卡丁和临床试验是合理的治疗选择；对于疾病复发时间>6 个月的患者，可考虑原始方案、拓扑替康或鲁比卡丁。此外，CD4/CD6 抑制剂 Trilaciclib 最近获得 FDA 批准，可降低 SCLC 患者化疗相关骨髓抑制的发生率。
虽然化疗免疫治疗在转移性疾病治疗中取得了适度的生存改善，但仍需要进一步研究以了解 SCLC 的生物学特性，从而为这种侵袭性疾病开发基于生物标志物的治疗策略和联合治疗方法。
