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avelumab+阿西替尼与舒尼替尼在治疗晚期肾细胞癌中的比较
作者:小柯机器人 发布时间:2020/9/12 13:31:19

美国丹娜-法伯癌症研究所Toni K. Choueiri、纪念斯隆-凯特琳癌症中心Robert J. Motzer等研究人员合作报道了avelumab+阿西替尼与舒尼替尼在治疗晚期肾细胞癌中的比较。相关论文于2020年9月7日在线发表在《自然—医学》杂志上。

研究人员报告了来自JAVELIN Renal 101三期临床试验(n=886;NCT02684006)基线肿瘤样品的分子分析的结果,该试验证明一线avelumab+阿西替尼与舒尼替尼在晚期肾细胞癌(aRCC)中显著延长了无进展生存期(PFS)。研究人员发现,在任一研究组中,既不表达通常评估的生物标志物PD-L1,也不表达肿瘤突变负担区分的PFS。同样,FcR单核苷酸多态性的存在也没有影响。
 
研究人员确定了与治疗组之间差异PFS相关的重要生物学特征,包括新的免疫调节和血管生成基因表达特征(GES)、先前未描述的突变概况及其对应的GES,以及几种HLA类型。这些发现提供了对PD-1/PD-L1和血管生成途径联合抑制反应决定因素的见解,并可能有助于开发改善aRCC患者的治疗策略。
 
附:英文原文

Title: Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial

Author: Robert J. Motzer, Paul B. Robbins, Thomas Powles, Laurence Albiges, John B. Haanen, James Larkin, Xinmeng Jasmine Mu, Keith A. Ching, Motohide Uemura, Sumanta K. Pal, Boris Alekseev, Gwenaelle Gravis, Matthew T. Campbell, Konstantin Penkov, Jae Lyun Lee, Subramanian Hariharan, Xiao Wang, Weidong Zhang, Jing Wang, Aleksander Chudnovsky, Alessandra di Pietro, Amber C. Donahue, Toni K. Choueiri

Issue&Volume: 2020-09-07

Abstract: We report on molecular analyses of baseline tumor samples from the phase 3 JAVELIN Renal 101 trial (n=886; NCT02684006), which demonstrated significantly prolonged progression-free survival (PFS) with first-line avelumab+axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We found that neither expression of the commonly assessed biomarker programmed cell death ligand 1 (PD-L1) nor tumor mutational burden differentiated PFS in either study arm. Similarly, the presence of FcR single nucleotide polymorphisms was unimpactful. We identified important biological features associated with differential PFS between the treatment arms, including new immunomodulatory and angiogenesis gene expression signatures (GESs), previously undescribed mutational profiles and their corresponding GESs, and several HLA types. These findings provide insight into the determinants of response to combined PD-1/PD-L1 and angiogenic pathway inhibition and may aid in the development of strategies for improved patient care in aRCC.

DOI: 10.1038/s41591-020-1044-8

Source: https://www.nature.com/articles/s41591-020-1044-8

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