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纳武单抗或纳武单抗联合伊匹单抗治疗可手术型非小细胞肺癌的2期临床试验结果
作者:小柯机器人 发布时间:2021/2/20 16:51:23

近日,美国德克萨斯大学安德森癌症中心Tina Cascone等研究人员报道了新辅助药物纳武单抗(nivolumab)或纳武单抗联合伊匹单抗(ipilimumab)治疗可手术型非小细胞肺癌的2期临床试验结果。这一研究成果于2021年2月18日在线发表在国际学术期刊《自然—医学》上。

研究人员报告了44例可手术的非小细胞肺癌(NSCLC)患者,以主要病理反应(MPR)为主要终点的新辅助药物纳武单抗或纳武单抗+伊匹单抗的2期随机NEOSTAR试验(NCT03158129)结果。针对新辅助化疗的历史对照测试了每个治疗组的MPR率。纳武单抗+伊匹单抗组达到了21位患者6例MPR的主要终点指标,达到38%的MPR率(8/21)。研究人员观察到纳武单抗组的MPR率为22%(5/23)。

在接受试验的37例患者中,纳武单抗和纳武单抗+伊匹单抗的MPR率分别为24%(5/21)和50%(8/16)。与纳武单抗相比,纳武单抗+伊匹单抗导致更高的病理完全缓解率(10%比38%),存活肿瘤更少(中位数50%比9%)以及效应子、组织驻留记忆和效应记忆T细胞的频率更高。肠道瘤胃球菌属(Ruminococcus)和Akkermansia菌属数量增加,这与MPR双重疗法相关。

这些数据表明,基于新辅助药物纳武单抗+伊匹单抗的疗法可增强病理反应、肿瘤免疫浸润和免疫记忆,并值得在可手术型NSCLC中进行进一步研究。 

据悉,伊匹单抗联合纳武单抗治疗转移性NSCLC时可改善临床结局,但尚不清楚其功效和对可手术型NSCLC免疫微环境的影响。

附:英文原文

Title: Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial

Author: Tina Cascone, William N. William, Annikka Weissferdt, Cheuk H. Leung, Heather Y. Lin, Apar Pataer, Myrna C. B. Godoy, Brett W. Carter, Lorenzo Federico, Alexandre Reuben, Md Abdul Wadud Khan, Hitoshi Dejima, Alejandro Francisco-Cruz, Edwin R. Parra, Luisa M. Solis, Junya Fujimoto, Hai T. Tran, Neda Kalhor, Frank V. Fossella, Frank E. Mott, Anne S. Tsao, George Blumenschein, Xiuning Le, Jianjun Zhang, Ferdinandos Skoulidis, Jonathan M. Kurie, Mehmet Altan, Charles Lu, Bonnie S. Glisson, Lauren Averett Byers, Yasir Y. Elamin, Reza J. Mehran, David C. Rice, Garrett L. Walsh, Wayne L. Hofstetter, Jack A. Roth, Mara B. Antonoff, Humam Kadara, Cara Haymaker, Chantale Bernatchez, Nadim J. Ajami, Robert R. Jenq, Padmanee Sharma, James P. Allison, Andrew Futreal, Jennifer A. Wargo, Ignacio I. Wistuba, Stephen G. Swisher, J. Jack Lee, Don L. Gibbons, Ara A. Vaporciyan, John V. Heymach, Boris Sepesi

Issue&Volume: 2021-02-18

Abstract: Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab+ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy. The nivolumab+ipilimumab arm met the prespecified primary endpoint threshold of 6 MPRs in 21 patients, achieving a 38% MPR rate (8/21). We observed a 22% MPR rate (5/23) in the nivolumab arm. In 37 patients resected on trial, nivolumab and nivolumab+ipilimumab produced MPR rates of 24% (5/21) and 50% (8/16), respectively. Compared with nivolumab, nivolumab+ipilimumab resulted in higher pathologic complete response rates (10% versus 38%), less viable tumor (median 50% versus 9%), and greater frequencies of effector, tissue-resident memory and effector memory T cells. Increased abundance of gut Ruminococcus and Akkermansia spp. was associated with MPR to dual therapy. Our data indicate that neoadjuvant nivolumab+ipilimumab-based therapy enhances pathologic responses, tumor immune infiltrates and immunologic memory, and merits further investigation in operable NSCLC.

DOI: 10.1038/s41591-020-01224-2

Source: https://www.nature.com/articles/s41591-020-01224-2

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex