Lu Hongyang, Jiang Zhiming
Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, China.
Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Adv Clin Exp Med. 2018 Sep;27(9):1317-1323. doi: 10.17219/acem/70159.
The proportion of small-cell lung cancer (SCLC) among all lung cancers decreased from 17.26% in 1986 to 12.95% in 2002. Chemotherapy is the key mode of treatment. However, novel therapeutic strategies and drugs are imperative, as the prognosis remains poor. In recent years, antibody therapies have shown promising prospects against malignancy. This review focuses on the advances in antibody therapies in SCLC. Although the results of pembrolizumab, nivolumab, ipilimumab, and rovalpituzumab tesirine are inspiring, all of the clinical trials on these drugs are phase I/II and have been verified for further phase III clinical trials. It was demonstrated that chemotherapy in combination with bevacizumab can improve the progression-free survival (PFS) in phase III trials. The insulin-like growth factor-1 receptor (IGF-1R) is associated with a poor prognosis in SCLC, while the anti-IGF-1R monoclonal antibody figitumumab has a potential therapeutic value. Tarextumab, an antibody that blocks both Notch2 and Notch3 signaling, in combination with etoposide and platinum (EP) in patients with untreated extensive-stage SCLC, proved to be well-tolerated and showed dosedependent anti-tumor activity. The therapeutic effect of sacituzumab govitecan, BW-2 and lorvotuzumab mertansine in SCLC warranted further evaluation. Bec2/BCG as an adjuvant vaccination in patients with limited-disease SCLC could not improve the survival, PFS, or quality of life. Thus, clinical studies are essential to confirm the anti-tumor efficacy of trastuzumab in SCLC.
小细胞肺癌（SCLC）在所有肺癌中的占比从1986年的17.26%降至2002年的12.95%。化疗是主要的治疗方式。然而，由于预后仍然较差，新型治疗策略和药物势在必行。近年来，抗体疗法在对抗恶性肿瘤方面显示出了广阔前景。本综述聚焦于SCLC抗体疗法的进展。尽管帕博利珠单抗、纳武利尤单抗、伊匹木单抗和罗伐匹妥珠单抗替西瑞的结果令人鼓舞，但所有关于这些药物的临床试验均处于I/II期，且已证实需进一步开展III期临床试验。在III期试验中已证明，化疗联合贝伐单抗可改善无进展生存期（PFS）。胰岛素样生长因子-1受体（IGF-1R）与SCLC的不良预后相关，而抗IGF-1R单克隆抗体西妥昔单抗具有潜在治疗价值。Tarextumab是一种可阻断Notch2和Notch3信号传导的抗体，在未治疗的广泛期SCLC患者中与依托泊苷和铂（EP）联合使用，耐受性良好且显示出剂量依赖性抗肿瘤活性。赛托珠单抗戈维汀、BW-2和洛伐替尼美坦新在SCLC中的治疗效果值得进一步评估。Bec2/BCG作为局限性疾病SCLC患者的辅助疫苗接种，无法提高生存率、PFS或生活质量。因此，临床研究对于证实曲妥珠单抗在SCLC中的抗肿瘤疗效至关重要。
