背景:免疫治疗联合化疗是广泛期小细胞肺癌(ES-SCLC)患者的一线治疗。越来越多的证据表明辐射,特别是立体定向身体放射治疗(SBRT),可以增强免疫原性反应以及细胞减少肿瘤负担。该研究的主要目的是确定接受多位点SBRT和化学免疫疗法联合治疗的新诊断ES-SCLC患者的无进展生存期(卡铂,依托泊苷,和durvalumab)。
方法:这是一个多中心,单臂,第二阶段研究。患者治疗-幼稚,ES-SCLC将有资格参加本研究。患者将接受durvalumab1500mgIVq3w,卡铂AUC5至6毫克/毫升q3w,和依托泊苷80至100毫克/平方米在第1天至3q3w四个周期,然后是durvalumab1500mg静脉q4w,直到疾病进展或不可接受的毒性。消融放射将分3或5个部分进行1至4个颅外部位。由位置决定,在周期2。主要终点是无进展生存期,从化学免疫疗法的第1天开始测量。次要终点包括RT后三个月内CTCAEv5.0的≥3级毒性,总生存率,响应率,二线系统治疗的时间,以及新的遥远进步的时间。
结论:现在免疫疗法已成为ES-SCLC管理的一个既定部分,重要的是进一步优化其使用和效果。这项研究将调查ES-SCLC患者SBRT和化学免疫疗法联合治疗的无进展生存期。此外,这项研究的数据可能进一步说明SBRT与化学免疫疗法的免疫原性作用,以及识别临床,生物,或放射学预后特征。
BACKGROUND: Immunotherapy in combination with chemotherapy is first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). Growing evidence suggests that radiation, specifically stereotactic body radiation therapy (SBRT), may enhance the immunogenic response as well as cytoreduce tumor burden. The primary objective of the study is to determine the progression free survival for patients with newly diagnosed ES-SCLC treated with combination multisite SBRT and chemo-immunotherapy (carboplatin, etoposide, and
durvalumab).
METHODS: This is a multicenter, single arm, phase 2
study. Patients with treatment-naïve, ES-SCLC will be eligible for this
study. Patients will receive
durvalumab 1500mg IV q3w, carboplatin AUC 5 to 6 mg/mL q3w, and etoposide 80 to 100 mg/m2 on days 1 to 3 q3w for four cycles, followed by
durvalumab 1500mg IV q4w until disease progression or unacceptable toxicity. Ablative radiation will be delivered 1 to 4 extracranial sites in 3 or 5 fractions, determined by location, during cycle 2. The primary endpoint is progression-free survival, measured from day 1 of chemoimmunotherapy. Secondary endpoints include grade ≥3 toxicity by CTCAE v5.0 within three months of RT, overall survival, response rate, time to second line systemic therapy, and time to new distant progression.
CONCLUSIONS: Now that immunotherapy is an established part of ES-SCLC management, it is important to further optimize its use and effect. This study will investigate the progression-free survival of combined SBRT and chemo-immunotherapy in patients with ES-SCLC. In addition, the data from this study may further inform the immunogenic role of SBRT with chemo-immunotherapy, as well as identify clinical, biological, or radiomic prognostic features.