西班牙马德里康普顿斯大学Luis Paz-Ares课题组取得一项新突破。他们探讨了Durvalumab联合铂-依托泊苷与铂-依托泊苷单用一线治疗广泛期小细胞肺癌（ES-SCLC）的效果。2019年10月4日，《柳叶刀》在线发表了这项成果。

2017年3月27日至2018年5月29日，这项随机、开放标签的临床3期试验在23个国家的209个地点进行，研究组招募了未经治疗的ES-SCLC成人患者，并将其随机分组。其中268名患者接受Durvalumab+铂-依托泊苷进行治疗，269名接受单独铂-依托泊苷治疗。

与铂-依托泊苷组相比，Durvalumab+铂-依托泊苷组的患者生存率显著提高，风险比为0.73。Durvalumab+铂-依托泊苷组的中位总生存期为13.0个月，铂-依托泊苷组为10.3个月；18个月时Durvalumab+铂-依托泊苷组患者的存活率为34%，铂-依托泊苷组为25%。两组中各有62%的患者发生3或4级严重不良事件，其中Durvalumab+铂-依托泊苷组中13例（5%）患者因此死亡，铂-依托泊苷组中有15例（6%）。

与临床相关的对照组相比，Durvalumab+铂-依托泊苷的一线疗法可显著改善ES-SCLC患者的总体生存率，且安全性调查结果与现有资料一致。

据悉，ES-SCLC患者的预后较差，近年来，免疫疗法治疗ES-SCLC展现出一定的临床潜力。

附：英文原文

Title: Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial

Author: Luis Paz-Ares, Mikhail Dvorkin, Yuanbin Chen, Niels Reinmuth, Katsuyuki Hotta, Dmytro Trukhin, Galina Statsenko, Maximilian J Hochmair, Mustafa zgürolu, Jun Ho Ji, Oleksandr Voitko, Artem Poltoratskiy, Santiago Ponce, Francesco Verderame, Libor Havel, Igor Bondarenko, Andrzej Kazarnowicz, Gyrgy Losonczy, Nikolay V Conev, Jon Armstrong, Natalie Byrne, Norah Shire, Haiyi Jiang, Jonathan W Goldman, for the CASPIAN investigators

Issue&Volume: 4 October 2019

Abstract: 

Background

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.

Methods

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 2 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 2 (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.

Findings

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.

Interpretation

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.

DOI: 10.1016/S0140-6736(19)32222-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32222-6/fulltext