Department of Medical Oncology, Hospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit, Universidad Complutense and Ciberonc, Madrid, Spain.
BHI of Omsk Region Clinical Oncology Dispensary, Omsk, Russia.
Lancet. 2019 Nov 23;394(10212):1929-1939. doi: 10.1016/S0140-6736(19)32222-6. Epub 2019 Oct 4.
Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum-etoposide) in treatment-naive patients with ES-SCLC.
This randomised, open-label, phase 3 trial was done at 209 sites across 23 countries. Eligible patients were adults with untreated ES-SCLC, with WHO performance status 0 or 1 and measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were randomly assigned (in a 1:1:1 ratio) to durvalumab plus platinum-etoposide; durvalumab plus tremelimumab plus platinum-etoposide; or platinum-etoposide alone. All drugs were administered intravenously. Platinum-etoposide consisted of etoposide 80-100 mg/m on days 1-3 of each cycle with investigator's choice of either carboplatin area under the curve 5-6 mg/mL per min or cisplatin 75-80 mg/m (administered on day 1 of each cycle). Patients received up to four cycles of platinum-etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks in the immunotherapy groups and up to six cycles of platinum-etoposide every 3 weeks plus prophylactic cranial irradiation (investigator's discretion) in the platinum-etoposide group. The primary endpoint was overall survival in the intention-to-treat population. We report results for the durvalumab plus platinum-etoposide group versus the platinum-etoposide group from a planned interim analysis. Safety was assessed in all patients who received at least one dose of their assigned study treatment. This study is registered at ClinicalTrials.gov, NCT03043872, and is ongoing.
Patients were enrolled between March 27, 2017, and May 29, 2018. 268 patients were allocated to the durvalumab plus platinum-etoposide group and 269 to the platinum-etoposide group. Durvalumab plus platinum-etoposide was associated with a significant improvement in overall survival, with a hazard ratio of 0·73 (95% CI 0·59-0·91; p=0·0047]); median overall survival was 13·0 months (95% CI 11·5-14·8) in the durvalumab plus platinum-etoposide group versus 10·3 months (9·3-11·2) in the platinum-etoposide group, with 34% (26·9-41·0) versus 25% (18·4-31·6) of patients alive at 18 months. Any-cause adverse events of grade 3 or 4 occurred in 163 (62%) of 265 treated patients in the durvalumab plus platinum-etoposide group and 166 (62%) of 266 in the platinum-etoposide group; adverse events leading to death occurred in 13 (5%) and 15 (6%) patients.
First-line durvalumab plus platinum-etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group. Safety findings were consistent with the known safety profiles of all drugs received.
AstraZeneca.
大多数小细胞肺癌（SCLC）患者在就诊时患有广泛期疾病，预后仍然较差。最近，免疫疗法在广泛期 SCLC（ES-SCLC）中显示出了临床疗效。CASPIAN 试验评估了 durvalumab 联合 tremelimumab 与依托泊苷联合顺铂或卡铂（铂类依托泊苷）在未经治疗的 ES-SCLC 患者中的疗效。
这是一项在 23 个国家的 209 个地点进行的随机、开放标签、III 期试验。合格的患者为未经治疗的 ES-SCLC 成年患者，WHO 表现状态为 0 或 1，根据实体瘤反应评估标准 1.1 版（Response Evaluation Criteria in Solid Tumors, version 1.1）可测量疾病。患者被随机分配（1:1:1 比例）至 durvalumab 联合铂类依托泊苷组；durvalumab 联合 tremelimumab 联合铂类依托泊苷组；或铂类依托泊苷组。所有药物均静脉给药。铂类依托泊苷由依托泊苷 80-100mg/m 组成，每个周期的第 1-3 天，研究者可选择卡铂曲线下面积 5-6mg/mL/分钟或顺铂 75-80mg/m（每个周期的第 1 天给药）。患者接受最多四个周期的铂类依托泊苷联合 durvalumab 1500mg 联合或不联合 tremelimumab 75mg，每 3 周一次，随后在免疫治疗组中每 4 周一次维持 durvalumab 1500mg，在铂类依托泊苷组中接受最多六个周期的铂类依托泊苷每 3 周一次加预防性颅脑照射（研究者决定）。主要终点是意向治疗人群的总生存期。我们报告了 durvalumab 联合铂类依托泊苷组与铂类依托泊苷组从计划的中期分析中的结果。在所有接受至少一剂研究治疗的患者中评估安全性。该研究在 ClinicalTrials.gov 注册，NCT03043872，正在进行中。
患者于 2017 年 3 月 27 日至 2018 年 5 月 29 日入组。268 名患者被分配至 durvalumab 联合铂类依托泊苷组，269 名患者被分配至铂类依托泊苷组。Durvalumab 联合铂类依托泊苷可显著改善总生存期，风险比为 0.73（95%CI 0.59-0.91；p=0.0047）；durvalumab 联合铂类依托泊苷组的中位总生存期为 13.0 个月（95%CI 11.5-14.8），铂类依托泊苷组为 10.3 个月（9.3-11.2），18 个月时存活患者比例分别为 34%（26.9-41.0）和 25%（18.4-31.6）。265 名接受治疗的患者中，有 163 名（62%）和 266 名（62%）患者发生任何级别 3 或 4 级不良事件，铂类依托泊苷组和铂类依托泊苷组分别有 13 名（5%）和 15 名（6%）患者因不良事件导致死亡。
一线 durvalumab 联合铂类依托泊苷显著改善了 ES-SCLC 患者的总生存期，与临床相关对照组相比具有显著改善。安全性结果与所有接受药物的已知安全性特征一致。
阿斯利康。
