The Real-world Therapeutic Analysis of First-line Immunotherapy in Chinese Patients with Drive Gene Positive for Advanced Non-Small Cell Lung Cancer.
The Real-world Therapeutic Analysis of First-line Immunotherapy in Chinese Patients with Drive Gene Positive for Advanced Non-Small Cell Lung Cancer.
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对晚期非小细胞肺癌呈阳性的中国驱动基因患者一线免疫疗法的现实治疗分析。
DOI：
10.7150/jca.77199
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发表时间：
2023
影响因子：
3.9
通讯作者：
Fu G
中科院分区：
文献类型：
--
作者：
Liu L;Li F;Zhao J;Zhuo X;Lai J;Wang J;Jiang F;Xu W;Luan F;Lin X;Yang S;Fu G
背景：免疫检查点抑制剂（ICIs）广泛用于晚期非小细胞肺癌（NSCLC）的治疗。然而，一些研究表明，基因突变患者不能从免疫治疗中获益。因此，本研究探讨了抗程序性死亡-1 （PD-1）和抗程序性死亡-配体-1 （PD-L1）抗体在现实世界中具有驱动基因突变的晚期NSCLC一线治疗中的疗效。方法：回顾性分析2019年5月至2020年10月山东省医院一线抗pd -1/PD-L1抗体治疗的晚期非小细胞肺癌患者。采用扩增难解突变系统PCR （ARMS-PCR）鉴定患者驱动基因突变状态。收集患者的基本临床特征、客观缓解率（ORR）、无进展生存期（PFS）等临床资料，评价驱动基因突变患者的临床疗效及潜在预后因素。结果：在此期间共统计430例患者信息，最终有89例NSCLC患者入组研究。主要病理亚型为腺癌（62.9%）。总突变率为44.9% (n = 40)，包括KRAS （n = 20）、TP53 （n = 18）、EGFR （n = 6）、BRAF （n = 3）、Her-2 （n = 3）、MET （n = 3）、ROS1 （n = 1）和NRAS （n = 1）突变。总ORR为44.30%，疾病控制率（DCR）为82.23%。在随访截止时，所有患者的中位PFS为8.2个月。在接受ICI治疗的NSCLC患者中，突变阴性患者的中位PFS长于突变阳性患者（8.98个月vs 7.07个月，P < 0.05）。不同突变亚组的生存获益不同：KRAS患者可以从一线免疫治疗中获益（10.1个月，P < 0.05）， EGFR突变患者的一线免疫治疗结果较差，中位PFS仅为3.0个月（P < 0.01），其他突变类型患者的应答与突变阴性患者无显著差异。在大多数突变亚组中，免疫联合治疗比免疫单药治疗的PFS更长，PD-L1表达水平与患者的临床获益呈正相关。结论：在现实世界中，KRAS突变患者受益于一线免疫治疗，免疫联合治疗方式更有效，免疫疗效与PD-L1表达呈正相关；其他驱动突变（BRAF、NRAS、Her2、MET、ROS1）患者在一线免疫治疗中的获益与突变阴性患者相似，推荐免疫治疗作为一线治疗；免疫治疗对EGFR突变的患者效果较差，即使是PD-L1高表达的患者，也不推荐在一线治疗中使用免疫治疗。
Background: Immune checkpoint inhibitors (ICIs) are widely used for treating advanced non-small cell lung cancer (NSCLC). However, some studies indicate that patients with genetic mutations do not benefit from immunotherapy. Hence, this study explored the efficacy of anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) antibodies in the first-line treatment of advanced NSCLC with driver gene mutations in real-world settings. Methods: We retrospective analyzed patients with advanced NSCLC who treated with first-line anti-PD-1/PD-L1 antibodies at Shandong Provincial Hospital between May 2019 and October 2020. The patient's driver gene mutation status was identified using amplification refractory mutation system PCR (ARMS-PCR). The basic clinical characteristics, objective response rate (ORR), progression free survival (PFS), and other clinical data of patients were collected to evaluate the clinical efficacy and potential prognostic factors of treatment for patients with driver gene mutations. Results: A total of 430 patients' information was counted during this period, finally, 89 patients with NSCLC were enrolled in the study. The main pathological subtype of patients was adenocarcinoma (62.9%). The overall mutation rate was 44.9% (n = 40) and included following mutations: KRAS (n = 20), TP53 (n = 18), EGFR (n = 6), BRAF (n = 3), Her-2 (n = 3), MET (n = 3), ROS1 (n = 1), and NRAS (n = 1). The overall ORR was 44.30% and the disease control rate (DCR) was 82.23%. At the time of follow-up cut-off, the median PFS of all patients was 8.2 month. In NSCLC patients treated with ICI, median PFS was longer in mutation-negative patients than in mutation-positive patients (8.98 vs 7.07 months, P < 0.05). Survival benefit varied across mutational subgroups: KRAS patients could benefit from first-line immunotherapy (10.1 months, P < 0.05), patients with EGFR mutations have poor first-line immunotherapy outcomes, with a median PFS of only 3.0 months (P < 0.01), and patients with other mutation types having no significant difference in response from mutation-negative patients. In most mutation subgroups, immune combination therapy had longer PFS than immune monotherapy, and PD-L1 expression levels were positively correlated with clinical benefit in patients. Conclusion: In the real world, patients with KRAS mutations benefit from first-line immunotherapy, immune-combination modalities are more effective, and immune efficacy is positively correlated with PD-L1 expression; Patients with other driver mutations (BRAF, NRAS, Her2, MET, ROS1) benefit similarly to mutation-negative patients in first-line immunotherapy, and immunotherapy is recommended for first-line therapy; Immunotherapy is worse effective in patients with EGFR mutations, immunotherapy is not recommended in first-line therapy even patients with high PD-L1 expression.
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影响因子：
7.3
作者：
Pinto JA;Vallejos CS;Raez LE;Mas LA;Ruiz R;Torres-Roman JS;Morante Z;Araujo JM;Gómez HL;Aguilar A;Bretel D;Flores CJ;Rolfo C
通讯作者：
Rolfo C
DOI：
10.1200/jco.20.01605
发表时间：
2021-03-01
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Borghaei H;Gettinger S;Vokes EE;Chow LQM;Burgio MA;de Castro Carpeno J;Pluzanski A;Arrieta O;Frontera OA;Chiari R;Butts C;Wójcik-Tomaszewska J;Coudert B;Garassino MC;Ready N;Felip E;García MA;Waterhouse D;Domine M;Barlesi F;Antonia S;Wohlleber M;Gerber DE;Czyzewicz G;Spigel DR;Crino L;Eberhardt WEE;Li A;Marimuthu S;Brahmer J
通讯作者：
Brahmer J
DOI：
10.1158/1078-0432.ccr-15-3101
发表时间：
2016-09-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Gainor JF;Shaw AT;Sequist LV;Fu X;Azzoli CG;Piotrowska Z;Huynh TG;Zhao L;Fulton L;Schultz KR;Howe E;Farago AF;Sullivan RJ;Stone JR;Digumarthy S;Moran T;Hata AN;Yagi Y;Yeap BY;Engelman JA;Mino-Kenudson M
通讯作者：
Mino-Kenudson M
影响因子：
5.6
作者：
Dantoing E;Piton N;Salaün M;Thiberville L;Guisier F
通讯作者：
Guisier F
影响因子：
254.7
作者：
Siegel, Rebecca L.;Miller, Kimberly D.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin