Patients With Short PFS to EGFR-TKIs Predicted Better Response to Subsequent Anti-PD-1/PD-L1 Based Immunotherapy in EGFR Common Mutation NSCLC.
Patients With Short PFS to EGFR-TKIs Predicted Better Response to Subsequent Anti-PD-1/PD-L1 Based Immunotherapy in EGFR Common Mutation NSCLC.
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DOI：
10.3389/fonc.2021.639947
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhou C
中科院分区：
文献类型：
--
作者：
Liu S;Wu F;Li X;Zhao C;Jia Y;Jia K;Han R;Qiao M;Li W;Yu J;Zhou F;Xiong A;Chen B;Fan J;Ren S;Zhou C
尽管单一免疫治疗的结果令人失望，但研究报告称，携带EGFR突变的非小细胞肺癌患者可能会从联合免疫治疗中受益。目前尚不清楚对先前EGFR-TKI的反应是否与后续免疫治疗的结果有关。对2016年1月至2019年6月接受ICI治疗的对EGFR-TKIs耐药的晚期非小细胞肺癌患者进行回顾性分析。采用单细胞测序和流式细胞术检测肿瘤微环境中细胞成分的差异。采用1：3配对病例对照研究，比较联合免疫治疗与标准化疗作为二线治疗的临床疗效。58例患者在EGFR-TKI治疗的基础上进行了抗PD-1/PD-L1免疫治疗。相关分析显示TKI-PFS与IO-PFS呈显著负相关(r=−0.35，p=0.006)。TKI-PFS截止10个月对后遗症免疫治疗有最显著的预测作用，经单因素和多因素分析证实为独立预测因素。Kaplan-Meier分析显示，TKI-PFS<10个月的患者IO-PFS显著延长(中位PFS为15.1vs3.8个月；HR为0.26，p=0.0002；ORR31.8vs10%，p=0.04)。单细胞RNA-SEQ显示，经EGFR-TKI治疗后，不同患者的细胞成分不同。流式细胞术证实，TKI-PFS较短的患者CD8效应细胞比例较高，M2/M1类巨噬细胞比例较低。病例对照研究显示，与传统化疗相比，联合免疫治疗可显著延长TKI-PFS患者的PFS(HR，0.51，95%CI：0.31~0.85，p=0.02)，延长OS(HR，0.48，95%CI：0.26~0.89，p=0.05)，提高ORR(33.3vs10.0%，p=0.02)。TKI-PFS短的患者比TKI-PFS长的患者对免疫治疗的反应更好。TME在这两个人群中的地位是不同的。对于TKI-PFS较短且没有T790M突变的患者，联合ICI治疗有望成为二线治疗中比经典化疗更好的选择。需要进一步探讨潜在的机制。
Despite disappointing outcomes from immuno-monotherapy, studies reported that NSCLC patients with EGFR mutation may possibly benefit from combined immunotherapy. Whether the response to prior EGFR-TKI has association with the outcomes of subsequent immunotherapy remains unclear. Advanced NSCLC patients with resistance to EGFR-TKIs and received ICI treatment from January 2016 to June 2019 were retrospectively analyzed. Single cell sequencing and flow cytometry were conducted to explore the difference of cell components in tumor microenvironments (TME). A 1:3 matched case–control study was conducted to compare the clinical effects of combined immunotherapy with standard chemotherapy as second-line treatment. Fifty-eight patients treated with anti-PD-1/PD-L1 based immunotherapy behind EGFR-TKI treatment were enrolled. Correlation analysis showed TKI-PFS had a significantly negative association with corresponding IO-PFS (r = −0.35, p = 0.006). TKI-PFS cutoff 10 months had the most significant predictive function for posterior immunotherapy and was validated to be an independent predictor by uni- and multivariate analyses. Kaplan–Meier analysis showed that patients with TKI-PFS less than 10 months had significantly prolonged IO-PFS and higher ORR than those with long (median PFS, 15.1 vs 3.8 months; HR, 0.26, p = 0.0002; ORR, 31.8 versus 10%, p = 0.04). Single cell RNA-seq revealed that the cell components were varied among patients after treatment with EGFR-TKI. Patients with short TKI-PFS demonstrated a relatively higher proportion of CD8 effector cells and lower ratio of M2 like macrophage to M1 like macrophages, which was validated by flow cytometry. Case–control study demonstrated that combined immunotherapy achieved significantly longer PFS (HR, 0.51, 95% CI: 0.31–0.85, p = 0.02), longer OS (HR, 0.48, 95% CI: 0.26–0.89, p = 0.05) and higher ORR (33.3 vs 10.0%, p = 0.02) than traditional chemotherapy for patients with short TKI-PFS. Patients with short TKI-PFS conferred better response to immunotherapy than those with long. The status of TME were different among those two populations. Combined ICI treatment could promisingly be a better choice than classical chemotherapy in second-line setting for patients with short TKI-PFS and no T790M mutation. Underlying mechanisms need to be further explored.
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DOI：
10.1016/j.jtho.2018.03.035
发表时间：
2018-08
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Lisberg A;Cummings A;Goldman JW;Bornazyan K;Reese N;Wang T;Coluzzi P;Ledezma B;Mendenhall M;Hunt J;Wolf B;Jones B;Madrigal J;Horton J;Spiegel M;Carroll J;Gukasyan J;Williams T;Sauer L;Wells C;Hardy A;Linares P;Lim C;Ma L;Adame C;Garon EB
通讯作者：
Garon EB
EGFR 靶向治疗改变 EGFR 驱动的肺部肿瘤的肿瘤微环境：联合治疗的意义
影响因子：
6.4
作者：
Jia, Yijun;Li, Xuefei;Zhou, Caicun
通讯作者：
Zhou, Caicun
联合放疗与抗PD-L1抗体协同增强非小细胞肺癌的抗肿瘤作用
影响因子：
20.4
作者：
Gong, Xiaomei;Li, Xuefei;Zhou, Caicun
通讯作者：
Zhou, Caicun
IV期或复发性非小细胞肺癌中的一线Nivolumab。
DOI：
10.1056/nejmoa1613493
发表时间：
2017-06-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Carbone DP;Reck M;Paz-Ares L;Creelan B;Horn L;Steins M;Felip E;van den Heuvel MM;Ciuleanu TE;Badin F;Ready N;Hiltermann TJN;Nair S;Juergens R;Peters S;Minenza E;Wrangle JM;Rodriguez-Abreu D;Borghaei H;Blumenschein GR Jr;Villaruz LC;Havel L;Krejci J;Corral Jaime J;Chang H;Geese WJ;Bhagavatheeswaran P;Chen AC;Socinski MA;CheckMate 026 Investigators
通讯作者：
CheckMate 026 Investigators
影响因子：
28.4
作者：
Bauml, Joshua M.;Mick, Rosemarie;Langer, Corey J.
通讯作者：
Langer, Corey J.