Liu Ming, Qiu Guihuan, Guan Wenhui, Xie Xiaohong, Lin Xinqing, Xie Zhanhong, Zhang Jiexia, Qin Yinyin, Du Haijian, Chen Xin, Deng Yu, Li Shiyue, Zhong Nanshan, Zhou Chengzhi
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Minimally Invasive Cancer Treatment Center, Guangdong Second Provincial General Hospital, Guangzhou, China.
Signal Transduct Target Ther. 2025 Feb 18;10(1):65. doi: 10.1038/s41392-025-02153-7.
Chemo-immunotherapy is the current first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC), but survival benefits are modest. We aimed to evaluate the safety, antitumor activity and biomarkers of first-line camrelizumab and apatinib plus chemotherapy in untreated ES-SCLC patients. In this single-arm trial (ClinicalTrials.gov NCT05001412), eligible patients received 2 cycles of etoposide and carboplatin (EC) as induction treatment followed by 2-4 cycles of camrelizumab, apatinib plus EC, then maintenance camrelizumab plus apatinib. Primary endpoint was safety. Secondary endpoints included objective response rate (ORR), duration of response, progression-free survival (PFS), and overall survival (OS). Targeted sequencing and whole transcriptome sequencing were performed to explore biomarkers. All enrolled 40 patients were treated and analyzed for safety. During the entire treatment, treatment-emergent adverse events (TEAEs) occurred in 40 patients (100%), and 30 (75.0%) were grade ≥3. The most common grade ≥3 TEAEs were neutropenia (35.0%), anemia (15.0%) and increased alanine aminotransferase (15.0%). No treatment-related deaths occurred. Among 36 evaluable patients, ORR was 88.9% (95% CI: 73.9%-96.9%), median PFS was 7.3 months (95% CI: 6.6-9.2) and median OS was 17.3 months (11.8-not reached). Mutations in RB1, high levels of tumor mutation burden, natural killer cells, and interferons, and low levels of cancer-associated fibroblasts, correlated with prolonged PFS. Induction chemotherapy followed by camrelizumab, apatinib plus EC demonstrated acceptable safety and promising antitumor activity in untreated ES-SCLC patients. The identified biomarkers need further validation.Trial Registration ClinicalTrials.gov Identifier: NCT05001412.
化疗免疫疗法是广泛期小细胞肺癌（ES-SCLC）患者目前的一线治疗方法，但生存获益有限。我们旨在评估一线卡瑞利珠单抗和阿帕替尼联合化疗在未经治疗的ES-SCLC患者中的安全性、抗肿瘤活性和生物标志物。在这项单臂试验（ClinicalTrials.gov NCT05001412）中，符合条件的患者接受2个周期的依托泊苷和卡铂（EC）作为诱导治疗，随后接受2 - 4个周期的卡瑞利珠单抗、阿帕替尼联合EC治疗，然后接受卡瑞利珠单抗联合阿帕替尼维持治疗。主要终点是安全性。次要终点包括客观缓解率（ORR）、缓解持续时间、无进展生存期（PFS）和总生存期（OS）。进行靶向测序和全转录组测序以探索生物标志物。所有入组的40例患者均接受治疗并进行安全性分析。在整个治疗期间，40例患者（100%）发生了治疗期间出现的不良事件（TEAE），其中30例（75.0%）为≥3级。最常见的≥3级TEAE是中性粒细胞减少（35.0%）、贫血（15.0%）和丙氨酸氨基转移酶升高（15.0%）。未发生与治疗相关的死亡。在36例可评估患者中，ORR为88.9%（95%CI：73.9%-96.9%），中位PFS为7.3个月（95%CI：6.6 - 9.2），中位OS为17.3个月（11.8 - 未达到）。RB1突变、高水平的肿瘤突变负荷、自然杀伤细胞和干扰素，以及低水平的癌症相关成纤维细胞，与PFS延长相关。诱导化疗后使用卡瑞利珠单抗、阿帕替尼联合EC在未经治疗的ES-SCLC患者中显示出可接受的安全性和有前景的抗肿瘤活性。所确定的生物标志物需要进一步验证。试验注册ClinicalTrials.gov标识符：NCT05001412。
