靶向藥Durvalumab聯(lián)合鉑-依托泊苷治療小細(xì)胞肺癌
2019-10-11
來(lái)源：小柯機(jī)器人
西班牙馬德里康普頓斯大學(xué)Luis Paz-Ares課題組取得一項(xiàng)新突破。他們探討了Durvalumab聯(lián)合鉑-依托泊苷與鉑-依托泊苷單用一線治療廣泛期小細(xì)胞肺癌（ES-SCLC）的效果。2019年10月4日，《柳葉刀》在線發(fā)表了這項(xiàng)成果。
2017年3月27日至2018年5月29日，這項(xiàng)隨機(jī)、開(kāi)放標(biāo)簽的臨床3期試驗(yàn)在23個(gè)國(guó)家的209個(gè)地點(diǎn)進(jìn)行，研究組招募了未經(jīng)治療的ES-SCLC成人患者，并將其隨機(jī)分組。其中268名患者接受Durvalumab+鉑-依托泊苷進(jìn)行治療，269名接受單獨(dú)鉑-依托泊苷治療。
與鉑-依托泊苷組相比，Durvalumab+鉑-依托泊苷組的患者生存率顯著提高，風(fēng)險(xiǎn)比為0.73。Durvalumab+鉑-依托泊苷組的中位總生存期為13.0個(gè)月，鉑-依托泊苷組為10.3個(gè)月；18個(gè)月時(shí)Durvalumab+鉑-依托泊苷組患者的存活率為34%，鉑-依托泊苷組為25%。兩組中各有62%的患者發(fā)生3或4級(jí)嚴(yán)重不良事件，其中Durvalumab+鉑-依托泊苷組中13例（5%）患者因此死亡，鉑-依托泊苷組中有15例（6%）。
與臨床相關(guān)的對(duì)照組相比，Durvalumab+鉑-依托泊苷的一線療法可改善ES-SCLC患者的總體生存率，且安全性調(diào)查結(jié)果與現(xiàn)有資料一致。
據(jù)悉，ES-SCLC患者的預(yù)后較差，近年來(lái)，免疫療法治療ES-SCLC展現(xiàn)出一定的臨床潛力。
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
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