a Department of Pulmonary Diseases, GROW - School for Oncology and Developmental Biology , Maastricht University Medical Centre , Maastricht , the Netherlands.
b Department of Medical Oncology, Gustave Roussy, Institut d'Oncologie Thoracique (IOT), Gustave Roussy , Université Paris-Saclay , Villejuif , France.
Expert Rev Anticancer Ther. 2019 Feb;19(2):151-167. doi: 10.1080/14737140.2019.1559057. Epub 2018 Dec 28.
: Small cell lung cancer (SCLC) is a tumor with a poor prognosis, often diagnosed in an advanced stage. Despite aggressive treatment of early and locally advanced disease, SCLC often relapses. First line chemotherapy provides good response rates in advanced disease, but progression free and overall survival are limited. New drugs such as some targeted therapies and immune therapies are promising in SCLC. : In this review, we discuss the preclinical rationale and trial data for targeted therapies and immune therapies in SCLC, with a specific focus on clinical trials. : Lack of identification of clear prognostic and predictive biomarkers has limited the advances in treatment efficacy. This has most likely been the main cause of failure for compounds tested so far. Due to the highly mutational profile and the rapid growth pattern of SCLC, immunotherapy combined with chemotherapy seems the most promising treatment option. Concerning targeted agents, achievements made so far are small, but DLL3-antibodies or combinations of PARPi and immunotherapy could be very promising. These promising strategies also need testing in limited disease.
小细胞肺癌(SCLC)是一种预后不良的肿瘤,通常在晚期诊断。尽管对早期和局部晚期疾病进行了积极治疗,但 SCLC 仍常复发。一线化疗可使晚期疾病获得良好的缓解率,但无进展生存期和总生存期有限。新的药物,如一些靶向治疗和免疫治疗,在 SCLC 中具有很大的希望。在这篇综述中,我们讨论了 SCLC 中靶向治疗和免疫治疗的临床前原理和临床试验数据,重点讨论了临床试验。缺乏明确的预后和预测生物标志物的识别限制了治疗效果的提高。这很可能是迄今为止测试的化合物失败的主要原因。由于 SCLC 的高度突变特征和快速生长模式,免疫治疗联合化疗似乎是最有前途的治疗选择。关于靶向药物,目前取得的成果很小,但 DLL3-抗体或 PARPi 与免疫治疗的联合可能非常有前途。这些有前途的策略也需要在有限的疾病中进行测试。