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新辅助纳武单抗加化疗治疗可切除肺癌可显著延长生存期
作者:小柯机器人 发布时间:2022/4/16 18:54:26

美国约翰霍普金斯金梅尔癌症中心Patrick M. Forde团队研究了新辅助纳武单抗联合化疗治疗可切除肺癌的疗效和安全性。2022年4月11日,《新英格兰医学杂志》发表了这一成果。

对于可切除的非小细胞肺癌(NSCLC),新辅助或辅助化疗与单纯手术相比有一定的益处。在早期试验中,基于纳武单抗的新辅助方案显示出了良好的临床活性;然而,需要3期临床试验的数据来证实这些发现。

在这项开放性的3期临床试验中,研究组将IB期至IIIA期可切除NSCLC的患者随机分为两组,分别接受纳武单抗联合铂类化疗或单纯铂类化疗,然后进行切除。主要终点为无事件生存率和病理完全缓解率(切除的肺和淋巴结中活瘤率为0%),均通过盲法独立评估。总体生存率是一个关键次要终点。对所有接受治疗的患者进行安全性评估。

纳武单抗联合化疗组的中位无事件生存期为31.6个月,显著高于单纯化疗组的20.8个月,疾病进展、疾病复发或死亡的危险比为0.63。纳武单抗联合化疗组中病理完全缓解的患者占24.0%,显著高于单纯化疗组的2.2%,优势比为13.94。

在大多数亚组中,无事件生存率和病理完全缓解的结果支持纳武单抗联合化疗而非单纯化疗。在第一次预先指定的中期分析中,死亡的危险比为0.57,不符合显著性标准。

在接受随机分组的患者中,纳武单抗联合化疗组中有83.2%接受了手术,单纯化疗组中有75.4%。纳武单抗联合化疗组中有33.5%的患者发生3级或4级治疗相关不良事件,单纯化疗组中有36.9%。

研究结果表明,在可切除的NSCLC患者中,与单纯化疗相比,新辅助纳武单抗加化疗可显著延长无事件生存期,且病理完全缓解的患者比例更高。在新辅助化疗中加入纳武单抗不会增加不良事件的发生率,也不会妨碍手术的可行性。

附:英文原文

Title: Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer | NEJM

Author: Patrick M. Forde, M.B., B.Ch.,, Jonathan Spicer, M.D., Ph.D.,, Shun Lu, M.D., Ph.D.,, Mariano Provencio, M.D., Ph.D.,, Tetsuya Mitsudomi, M.D., Ph.D.,, Mark M. Awad, M.D., Ph.D.,, Enriqueta Felip, M.D., Ph.D.,, Stephen R. Broderick, M.D., M.P.H.S.,, Julie R. Brahmer, M.D.,, Scott J. Swanson, M.D.,, Keith Kerr, M.B., Ch.B.,, Changli Wang, M.D., Ph.D.,, Tudor-Eliade Ciuleanu, M.D., Ph.D.,, Gene B. Saylors, M.D.,, Fumihiro Tanaka, M.D., Ph.D.,, Hiroyuki Ito, M.D., Ph.D.,, Ke-Neng Chen, M.D.,, Moishe Liberman, M.D., Ph.D.,, Everett E. Vokes, M.D.,, Janis M. Taube, M.D.,, Cecile Dorange, M.S.,, Junliang Cai, M.D.,, Joseph Fiore, Pharm.D.,, Anthony Jarkowski, Pharm.D.,, David Balli, Ph.D.,, Mark Sausen, Ph.D.,, Dimple Pandya, M.D.,, Christophe Y. Calvet, Ph.D.,, and Nicolas Girard, M.D., Ph.D.

Issue&Volume: 2022-04-11

Abstract:

Background

Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non–small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.

Methods

In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients.

Results

The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P=0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group.

Conclusions

In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery.

DOI: 10.1056/NEJMoa2202170

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2202170

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home