Chen Dawei, Zou Bing, Li Butuo, Gao Aiqin, Huang Wei, Shao Qian, Meng Xiangjiao, Zhang Pinliang, Tang Xiaoyong, Hu Xudong, Zhang Yan, Guo Jun, Zhao Changhong, Yuan Jiajia, Li Qian, Zhu Changbin, Yu Jinming, Wang Linlin
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China.
EClinicalMedicine. 2024 Aug 21;75:102795. doi: 10.1016/j.eclinm.2024.102795. eCollection 2024 Sep.
This phase II prospective trial aimed to investigate the efficacy and safety of adebrelimab (PD-L1 antibody) plus first-line chemotherapy followed by sequential thoracic radiotherapy (TRT) combined with adebrelimab in extensive-stage small-cell lung cancer (ES-SCLC). Biomarkers associated with potential therapeutic effects were also explored.
Patients with previously untreated ES-SCLC were enrolled at Shandong Cancer Hospital and Institute (Jinan, China). Patients received 4-6 cycles of adebrelimab (20 mg/kg, D1, Q3W) combined with EP/EC (etoposide, 100 mg/m, D1-3, Q3W and cisplatin, 75 mg/m, D1, Q3W or carboplatin, AUC = 5, D1, Q3W). Then patients with response sequentially underwent consolidative TRT (≥30 Gy in 10 fractions or ≥50 Gy in 25 fractions, involved-field irradiation), and maintenance adebrelimab until disease progression or intolerable adverse events (AEs). The primary endpoint was overall survival (OS). Genomic and circulating tumour DNA (ctDNA) profiling were also analyzed with tumour tissues and peripheral blood. This trial was registered with ClinicalTrials.gov, NCT04562337.
From October 2020 to April 2023, 67 patients diagnosed with ES-SCLC were enrolled and received at least one dose of study treatment. All patients were included in the efficacy and safety analyses. 45 patients received sequential TRT as planned. The median OS and progression-free survival (PFS) was 21.4 months (95% CI: 17.2-not reached months) and 10.1 months (95% CI: 6.9-15.5 months), respectively. The confirmed objective response rate was 71.6% (48/67, 95% CI: 59.3-82.0%) and disease control rate was 89.6% (60/67, 95% CI: 79.7-95.7%). There were no treatment-related deaths. The most common grade 3 or higher treatment-related adverse events (TRAEs) were hematological toxicities. The incidence of any grade and G3+ pneumonitis was 25% (17/67) and 6% (4/67), respectively. No unexpected adverse events were observed. Patients without co-mutations of TP53/RB1 in both tissue and peripheral blood displayed longer PFS (tissue, P = 0.071; ctDNA, P = 0.060) and OS (tissue, P = 0.032; ctDNA, P = 0.031).
Adebrelimab plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety.
This study was funded by the National Natural Science Foundation of China (82172865), Jiangsu Hengrui Pharmaceuticals Co., Ltd. and Amoy Diagnostics Co., Ltd.
本II期前瞻性试验旨在研究阿得贝利单抗（一种程序性死亡配体1抗体）联合一线化疗，随后序贯胸部放疗（TRT）并联合阿得贝利单抗用于广泛期小细胞肺癌（ES-SCLC）的疗效和安全性。同时也探索了与潜在治疗效果相关的生物标志物。
既往未接受过治疗的ES-SCLC患者在山东省肿瘤医院暨山东省肿瘤防治研究院（中国济南）入组。患者接受4-6周期的阿得贝利单抗（20mg/kg，第1天，每3周一次）联合EP/EC方案（依托泊苷，100mg/m²，第1-3天，每3周一次；顺铂，75mg/m²，第1天，每3周一次或卡铂，曲线下面积=5，第1天，每3周一次）。然后，缓解的患者序贯接受巩固性TRT（10次分割，总剂量≥30Gy或25次分割，总剂量≥50Gy，累及野照射），并持续使用阿得贝利单抗维持治疗，直至疾病进展或出现无法耐受的不良事件（AE）。主要终点为总生存期（OS）。还对肿瘤组织和外周血进行了基因组和循环肿瘤DNA（ctDNA）分析。本试验已在ClinicalTrials.gov注册，注册号为NCT04562337。
2020年10月至2023年4月，67例确诊为ES-SCLC的患者入组并接受了至少一剂研究治疗。所有患者均纳入疗效和安全性分析。45例患者按计划接受了序贯TRT。中位总生存期和无进展生存期（PFS）分别为21.4个月（95%CI：17.2-未达到个月）和10.1个月（95%CI：6.9-15.5个月）。确认的客观缓解率为71.6%（48/67，95%CI：59.3-82.0%），疾病控制率为89.6%（60/67，95%CI：79.7-95.7%）。无治疗相关死亡。最常见的3级或更高等级的治疗相关不良事件（TRAEs）为血液学毒性。任何等级和3级及以上肺炎的发生率分别为25%（17/67）和6%（4/67）。未观察到意外不良事件。组织和外周血中均无TP53/RB1共突变的患者显示出更长的PFS（组织，P=0.071；ctDNA，P=0.060）和OS（组织，P=0.032；ctDNA，P=0.031）。
阿得贝利单抗联合化疗及序贯TRT作为ES-SCLC的一线治疗显示出有前景的疗效和可接受的安全性。
本研究由中国国家自然科学基金（82172865）、江苏恒瑞医药股份有限公司和厦门艾德生物医药科技股份有限公司资助。
