卡铂、依托泊苷、阿替利珠单抗和贝伐单抗用于广泛期小细胞肺癌患者的一线治疗：GOIRC-01-2019 CeLEBrATE研究
Carboplatin, etoposide, atezolizumab, and bevacizumab in the first-line treatment of patients with extensive stage small-cell lung cancer: the GOIRC-01-2019 CeLEBrATE study.
作者信息
Lamberti Giuseppe, Rihawi Karim, Mazzoni Francesca, Riccardi Ferdinando, Follador Alessandro, Tiseo Marcello, Frassoldati Antonio, Colantonio Ida, Bonetti Andrea, Genova Carlo, Giardina Donatella, Bertolini Federica, Cinieri Saverio, Pasello Giulia, Brighenti Matteo, Andrini Elisa, Tognetto Michele, Boni Luca, Ardizzoni Andrea
机构信息
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
出版信息
J Immunother Cancer. 2025 May 7;13(5):e010694. doi: 10.1136/jitc-2024-010694.
BACKGROUND
The addition of a programmed death-ligand 1 (PD-L1) inhibitor, either atezolizumab or durvalumab, to platinum-etoposide prolonged survival in a limited subset of patients with extensive-stage small-cell lung cancer (ES-SCLC). Preclinical studies demonstrated synergistic antitumor activity of combined vascular endothelial growth factor receptor and PD-L1 inhibition in SCLC. Since bevacizumab added to platinum-etoposide was safe and active in ES-SCLC, we investigated the efficacy of atezolizumab, bevacizumab, carboplatin, and etoposide as first-line treatment of ES-SCLC.
METHODS
The CeLEBrATE study is an Italian multicentric single-arm phase II trial of carboplatin (area under the curve 5 ml/min), etoposide (100 mg/sqm), bevacizumab (7.5 mg/kg), and atezolizumab (1,200 mg) every 3 weeks (q3w) for four to six courses, followed by bevacizumab and atezolizumab maintenance q3w in patients with ES-SCLC and no contraindications to immunotherapy or antiangiogenic therapy. Patients with asymptomatic brain metastases were eligible. Prophylactic cranial irradiation and consolidation thoracic external radiotherapy were not permitted while on study treatment. Primary endpoint was overall survival (OS) rate at 1 year.
RESULTS
53 patients were enrolled (45.3% women, median age 65 years) and received at least one dose of study treatment. At a median follow-up time of 23.4 months (95% CI: 21.1 to 26.0), the 1-year OS rate was 61.8% (90% CI: 50.7% to 72.8%; p=0.04), with a median OS of 12.9 months (95% CI: 11.6 to 17.5). Median progression-free survival was 6.2 months (95% CI: 5.4 to 6.6) and objective response rate was 83.3% (95% CI: 69.8% to 92.5%). Grade 3-4 adverse events were reported in 34 patients (64.2%) leading to dose reductions in 24 (45.3%), and dose delays in 39 (73.9%) and 32 (69.6%) during the induction and maintenance phase, respectively. 19 (35.8%) treatment-related serious adverse events were reported.
CONCLUSION
The CeLEBrATE study met its primary objective demonstrating a signal of efficacy of bevacizumab, atezolizumab, carboplatin, and etoposide in the first-line treatment of patients with ES-SCLC.
TRIAL REGISTRATION NUMBER
GOIRC-01-2019 ML41241, Eudract Number: 2019-003798-2.
背景
在广泛期小细胞肺癌（ES-SCLC）患者的有限亚组中，将程序性死亡配体1（PD-L1）抑制剂阿替利珠单抗或度伐利尤单抗添加到铂类-依托泊苷方案中可延长生存期。临床前研究表明，在小细胞肺癌中联合抑制血管内皮生长因子受体和PD-L1具有协同抗肿瘤活性。由于在ES-SCLC中，将贝伐单抗添加到铂类-依托泊苷方案中是安全且有效的，因此我们研究了阿替利珠单抗、贝伐单抗、卡铂和依托泊苷作为ES-SCLC一线治疗方案的疗效。
方法
CeLEBrATE研究是一项意大利多中心单臂II期试验，每3周（q3w）给予卡铂（曲线下面积5 ml/min）、依托泊苷（100 mg/sqm）、贝伐单抗（7.5 mg/kg）和阿替利珠单抗（1200 mg），共进行4至6个疗程，随后对无免疫治疗或抗血管生成治疗禁忌证的ES-SCLC患者每3周进行贝伐单抗和阿替利珠单抗维持治疗。无症状脑转移患者符合入组条件。在研究治疗期间不允许进行预防性颅脑照射和巩固性胸部外照射。主要终点是1年总生存率（OS）。
结果
53例患者入组（45.3%为女性，中位年龄65岁）并接受了至少一剂研究治疗。中位随访时间为23.4个月（95%CI：21.1至26.0），1年OS率为61.8%（90%CI：50.7%至72.8%；p=0.04），中位OS为12.9个月（95%CI：11.6至17.5）。中位无进展生存期为6.2个月（95%CI：5.4至6.6），客观缓解率为83.3%（95%CI：69.8%至92.5%）。34例患者（64.2%）报告了3-4级不良事件，导致24例（45.3%）剂量减少，诱导期和维持期分别有39例（73.9%）和32例（69.6%）出现剂量延迟。报告了19例（35.8%）与治疗相关的严重不良事件。
结论
CeLEBrATE研究达到了其主要目标，证明了贝伐单抗、阿替利珠单抗、卡铂和依托泊苷在ES-SCLC患者一线治疗中的疗效信号。
试验注册号
GOIRC-01-2019 ML41241，欧盟临床试验编号：2019-003798-2。
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