荷兰癌症研究所Paul Baas团队研究了纳武单抗联合伊匹单抗一线治疗不能切除的恶性胸膜间皮瘤对患者预后的影响。2021年1月21日，该研究发表在《柳叶刀》杂志上。
恶性胸膜间皮瘤（MPM）经批准的全身治疗仅限于化疗方案，这些方案具有中等的生存获益，但预后较差。纳武单抗联合伊匹单抗在其他肿瘤类型，包括一线非小细胞肺癌中显示出临床益处。研究组假设这个方案可以提高MPM患者的总生存率。
研究组在21个国家的103家医院进行了一项开放标签、随机、临床3期研究，招募年龄为18岁及以上，先前未经治疗，组织学证实不能切除的MPM，东部肿瘤合作组的表现状态为0或1的患者。将这些患者按1：1随机分配，分别接受纳武单抗联合伊匹单抗治疗，长达2年；或接受铂联合培美曲塞化疗，每3周一次，最多6个周期。主要终点是所有参与者的总生存率，并对至少接受一剂研究治疗的所有参与者进行安全性评估。
2016年11月29日至2018年4月28日，共有713名患者入组，其中605名患者接受随机分配，纳武单抗+伊匹单抗组303例，化疗组302例。605名参与者中467名（77%）为男性，中位年龄为69岁。在预先指定的中期分析中，中位随访29.7个月后，纳武单抗+伊匹单抗组的中位总生存期为18.1个月，显著长于化疗组（14.1个月），风险比为0.74。
纳武单抗+伊匹单抗组的2年总生存率为41%，化疗组为27%。纳武单抗+伊匹单抗组的300例患者中有91例（30%）出现3-4级治疗相关的不良事件，化疗组的284例患者中有91例（32%）。纳武单抗+伊匹单抗组中有3例（1%）发生治疗相关的死亡（肺炎、脑炎和心力衰竭），化疗组有1例（骨髓抑制）。
研究结果表明，对于先前未经治疗的不可切除的MPM患者，采用纳武单抗联合伊匹单抗治疗，与标准化疗方案相比，可显著改善总体生存率。
附：英文原文
Title: First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial
Author: Paul Baas, Arnaud Scherpereel, Anna K Nowak, Nobukazu Fujimoto, Solange Peters, Anne S Tsao, Aaron S Mansfield, Sanjay Popat, Thierry Jahan, Scott Antonia, Youssef Oulkhouir, Yolanda Bautista, Robin Cornelissen, Laurent Greillier, Francesco Grossi, Dariusz Kowalski, Jerónimo Rodríguez-Cid, Praveen Aanur, Abderrahim Oukessou, Christine Baudelet, Gérard Zalcman
Issue&Volume: 2021-01-21
Abstract:
Background
Approved systemic treatments for malignant pleural mesothelioma (MPM) have been limited to chemotherapy regimens that have moderate survival benefit with poor outcomes. Nivolumab plus ipilimumab has shown clinical benefit in other tumour types, including first-line non-small-cell lung cancer. We hypothesised that this regimen would improve overall survival in MPM.
Methods
This open-label, randomised, phase 3 study (CheckMate 743) was run at 103 hospitals across 21 countries. Eligible individuals were aged 18 years and older, with previously untreated, histologically confirmed unresectable MPM, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to nivolumab (3 mg/kg intravenously once every 2 weeks) plus ipilimumab (1 mg/kg intravenously once every 6 weeks) for up to 2 years, or platinum plus pemetrexed chemotherapy (pemetrexed [500 mg/m 2 intravenously] plus cisplatin [75 mg/m 2 intravenously] or carboplatin [area under the concentration-time curve 5 mg/mL per min intravenously]) once every 3 weeks for up to six cycles. The primary endpoint was overall survival among all participants randomly assigned to treatment, and safety was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT02899299, and is closed to accrual.
Findings
Between Nov 29, 2016, and April 28, 2018, 713 patients were enrolled, of whom 605 were randomly assigned to either nivolumab plus ipilimumab (n=303) or chemotherapy (n=302). 467 (77%) of 605 participants were male and median age was 69 years (IQR 64–75). At the prespecified interim analysis (database lock April 3, 2020; median follow-up of 29·7 months [IQR 26·7–32·9]), nivolumab plus ipilimumab significantly extended overall survival versus chemotherapy (median overall survival 18·1 months [95% CI 16·8–21·4] vs 14·1 months [12·4–16·2]; hazard ratio 0·74 [96·6% CI 0·60–0·91]; p=0·0020). 2-year overall survival rates were 41% (95% CI 35·1–46·5) in the nivolumab plus ipilimumab group and 27% (21·9–32·4) in the chemotherapy group. Grade 3–4 treatment-related adverse events were reported in 91 (30%) of 300 patients treated with nivolumab plus ipilimumab and 91 (32%) of 284 treated with chemotherapy. Three (1%) treatment-related deaths occurred in the nivolumab plus ipilimumab group (pneumonitis, encephalitis, and heart failure) and one (<1%) in the chemotherapy group (myelosuppression).
Interpretation
Nivolumab plus ipilimumab provided significant and clinically meaningful improvements in overall survival versus standard-of-care chemotherapy, supporting the use of this first-in-class regimen that has been approved in the USA as of October, 2020, for previously untreated unresectable MPM.
DOI: 10.1016/S0140-6736(20)32714-8
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32714-8/fulltext
LANCET：《柳叶刀》，创刊于1823年。隶属于爱思唯尔出版社，最新IF：202.731
官方网址：http://www.thelancet.com/
投稿链接：http://ees.elsevier.com/thelancet
本期文章：《柳叶刀》：Online/在线发表
