Front Oncol:TMB状态对抗HER2治疗在HER2阳性晚期胃癌(AGC)的疗效的影响

2021-12-04 yd2015 MedSci原创

研究表明,TMB的状态可能是预测曲妥珠单抗联合化疗治疗HER2阳性AGC患者疗效的一个新的生物标志物。

曲妥珠单抗(Trastuzumab)是一种靶向her2的人源化单克隆抗体,已被推荐作为HER2阳性晚期胃癌(AGC)患者的一线治疗药物。但是,根据肿瘤突变负荷(tumor mutant burden, TMB)状态HER2阳性AGC进行抗HER2治疗的效果尚不清楚近期,韩国学者开展了相关研究,根据TMB状态评估抗HER2治疗在HER2阳性AGC的疗效。相关结果发表在Frontiers in Oncology杂志上。

研究对31HER2阳性的AGC患者进行了下一代测序(NGS),包括TMB分析,这些患者接受曲妥珠单抗加化疗作为一线治疗,包括复发(n=8)或转移(n=23)肿瘤患者。

纳入的31例患者,中位年龄57.0岁(范围35-76),男性25人(80.6%),女性6人(19.4%)。24例(77.4%)确诊为管状腺癌,16例(51.6%)分化程度中等。所有患者均为微卫星稳定型(MSS)。30例(96.8%)为IHC 3+肿瘤,仅有1例为IHC 2+和SISH阳性肿瘤。低TMB患者27例(87.1%),高TMB患者4例(12.9%)。在TMB-low组中只有1例患者EB病毒(EBV)阳性。15例(48.4%)患者PD-L1阳性,包括高TMB组1例和低TMB组14例。23例(74.2%)患者首次诊断为转移性AGC。

             临床特征

中位随访时间为10.8个月(范围为1.7- 20.9)。治疗周期中位数为7.0(范围,2- 20),治疗持续时间中位数为4.7个月(范围,0.7-14.2)。所有患者的ORR为61.3%,其中CR 1例(3.2%),PR 18例(58.1%)。4例(12.9%)患者病情稳定(SD), 4例(12.9%)患者病情进展(PD)。在4例高TMB患者中,3例达到CR或PR,另1例由于治疗时间短,未评估肿瘤反应。27例低TMB患者中ORR为59.3%,4例(14.8%)为PD。高TMB患者(75%,n=3/4)与低TMB患者(59.3%,n=16/27)相比,曲妥珠单抗加化疗的ORR趋于更高。

              疗效评估

CR或PR患者的中位DOR为6.1个月(IQR, 3.4-9.6)。所有患者的中位PFS为9.0个月(95%CI, 7.1-10.8),中位OS尚未达到。

               所有患者的PFS和OS

根据TMB状态,高TMB患者的中位PFS尚未达到,低TMB患者的中位PFS为8.0个月(95% CI, 7.6-8.5) (HR= 0.122;95%CI, 0.016- 0.954,P = 0.019)。高TMB患者的中位OS尚未达到,低TMB患者的中位OS为14.5个月(95% CI, 10.3-18.7) (HR, 0.034;95% CI, 0- 31.208,P=0.117)。

           高低TMB患者的PFS和OS

综上,研究表明,TMB的状态可能是预测曲妥珠单抗联合化疗治疗HER2阳性AGC患者疗效的一个新的生物标志物。

原始出处:

Kim HR, Ahn S, Jo H, Kim H, Hong J, Lee J, Lim H-Y, Kang WK and Kim ST (2021) The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers. Front. Oncol. 11:792340. doi: 10.3389/fonc.2021.792340

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    2022-10-18 minlingfeng
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    2021-12-05 hsboy

    是否her-2加免疫

    0

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    2021-12-04 杨饱饱

    TMB的状态可能是预测曲妥珠单抗联合化疗治疗HER2阳性AGC患者疗效的一个新的生物标志物。#肿瘤#

    0