可手术的非小细胞肺癌的新辅助化疗加nivolumab与或不加ipilimumab：2期平台NEOSTAR试验

SCI 30 March 2023

Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial

 (Nat Med IF: 53.44)

Cascone T, Leung CH, Weissferdt A, Pataer A, Carter BW, Godoy MCB, Feldman H, William WN Jr, Xi Y, Basu S, Sun JJ, Yadav SS, Rojas Alvarez FR, Lee Y, Mishra AK, Chen L, Pradhan M, Guo H, Sinjab A, Zhou N, Negrao MV, Le X, Gay CM, Tsao AS, Byers LA, Altan M, Glisson BS, Fossella FV, Elamin YY, Blumenschein G Jr, Zhang J, Skoulidis F, Wu J, Mehran RJ, Rice DC, Walsh GL, Hofstetter WL, Rajaram R, Antonoff MB, Fujimoto J, Solis LM, Parra ER, Haymaker C, Wistuba II, Swisher SG, Vaporciyan AA, Lin HY, Wang J, Gibbons DL, Jack Lee J, Ajami NJ, Wargo JA, Allison JP, Sharma P, Kadara H, Heymach JV, Sepesi B. Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial. Nat Med. 2023 Mar;29(3):593-604. doi: 10.1038/s41591-022-02189-0. Epub 2023 Mar 16. PMID: 36928818; PMCID: PMC10033402.

Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEOSTAR trial testing neoadjuvant Nivo+CT and Ipi+Nivo+CT with major pathologic response (MPR) as the primary endpoint. MPR rates were 32.1% (7/22, 80% confidence interval (CI) 18.7–43.1%) in the Nivo+CT arm and 50% (11/22, 80% CI 34.6–61.1%) in the Ipi+Nivo+CT arm; the primary endpoint was met in both arms. In patients without known tumor EGFR/ALK alterations, MPR rates were 41.2% (7/17) and 62.5% (10/16) in the Nivo+CT and Ipi+Nivo+CT groups, respectively. No new safety signals were observed in either arm. Single-cell sequencing and multi-platform immune profiling (exploratory endpoints) underscored immune cell populations and phenotypes, including effector memory CD8+ T, B and myeloid cells and markers of tertiary lymphoid structures, that were preferentially increased in the Ipi+Nivo+CT cohort. Baseline fecal microbiota in patients with MPR were enriched with beneficial taxa, such as Akkermansia, and displayed reduced abundance of pro-inflammatory and pathogenic microbes. Neoadjuvant Ipi+Nivo+CT enhances pathologic responses and warrants further study in operable NSCLC.

在可手术的非小细胞肺癌（NSCLC）患者中，新辅助治疗ipilimumab+nivolumab（Ipi+Nivo）和nivolumab+化疗（Nivo+CT）比单独使用CT诱发更大的病理反应率。在新辅助Nivo+CT中加入ipilimumab的影响尚不清楚。在此，我们报告了2期平台NEOSTAR试验的两组结果和相关情况，测试新辅助Nivo+CT和Ipi+Nivo+CT，主要病理反应（MPR）为主要终点。Nivo+CT组的MPR率为32.1%（7/22，80%置信区间（CI）为18.7-43.1%），Ipi+Nivo+CT组为50%（11/22，80%CI为34.6-61.1%）；两个组均达到主要终点。在没有已知肿瘤EGFR/ALK改变的患者中，Nivo+CT和Ipi的MPR率分别为41.2%（7/17）和62.5%（10/16）。Nivo+CT组和Ipi+Nivo+CT组的MPR率分别为41.2%（7/17）和62.5%（10/16）。两组中均未观察到新的安全信号。单细胞测序和多平台免疫分析（探索性终点）强调了免疫细胞群和表型，包括效应记忆CD8+T、B和骨髓细胞以及三级淋巴结构的标志物，在Ipi+Nivo+CT队列中优先增加。MPR患者的基线粪便微生物群富含有益的分类群，如Akkermansia，并显示促炎症和致病微生物的丰度降低。新辅助Ipi+Nivo+CT可增强病理反应，值得对可手术的NSCLC进行进一步研究。

打赏