■这项II期前瞻性试验旨在研究在广泛期小细胞肺癌(ES-SCLC)中,使用adebrelimab(PD-L1抗体)加一线化疗,然后序贯胸部放疗(TRT)联合adebrelimab的疗效和安全性。还探索了与潜在治疗效果相关的生物标志物。
■先前未经治疗的ES-SCLC患者在山东省肿瘤医院和研究所(济南,中国)。患者接受4-6个周期的adebrelimab(20mg/kg,D1,Q3W)与EP/EC(依托泊苷,100mg/m2,D1-3,Q3W和顺铂,75mg/m2,D1,Q3W或卡铂,AUC=5,D1,Q3W)。然后,有反应的患者依次接受合并TRT(10个分数≥30Gy或25个分数≥50Gy,涉及场辐照),和维持adebrelimab直到疾病进展或不可耐受的不良事件(AE)。主要终点是总生存期(OS)。还用肿瘤组织和外周血分析了基因组和循环肿瘤DNA(ctDNA)谱分析。该试验已在ClinicalTrials.gov注册,NCT04562337。
■从2020年10月至2023年4月,纳入了67例诊断为ES-SCLC的患者,并接受了至少一个剂量的研究治疗。所有患者均纳入疗效和安全性分析。45例患者按计划接受序贯TRT。中位OS和无进展生存期(PFS)为21.4个月(95%CI:17.2-未达到月)和10.1个月(95%CI:6.9-15.5个月),分别。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%)。没有治疗相关的死亡。最常见的3级或更高级别治疗相关不良事件(TRAEs)是血液毒性。任何级别和G3+肺炎的发生率分别为25%(17/67)和6%(4/67),分别。没有观察到意外的不良事件。组织和外周血中没有TP53/RB1共突变的患者显示更长的PFS(组织,P=0.071;ctDNA,P=0.060)和OS(组织,P=0.032;ctDNA,P=0.031)。
■Adebrelimab联合化疗和序贯TRT作为ES-SCLC的一线治疗显示出良好的疗效和可接受的安全性。
■本研究由国家自然科学基金(82172865)资助,江苏恒瑞医药有限公司有限公司和淘品诊断有限公司,Ltd.
UNASSIGNED: 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.
UNASSIGNED: 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/m2, D1-3, Q3W and cisplatin, 75 mg/m2, 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.
UNASSIGNED: 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).
UNASSIGNED: Adebrelimab plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety.
UNASSIGNED: This study was funded by the National Natural Science Foundation of China (82172865), Jiangsu Hengrui Pharmaceuticals Co., Ltd. and Amoy Diagnostics Co., Ltd.