Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry
Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry
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DOI：
10.1093/annonc/mdz167
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发表时间：
2019-08-01
影响因子：
50.5
通讯作者：
Gautschi, O.
中科院分区：
文献类型：
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作者：
Mazieres, J.;Drilon, A.;Gautschi, O.
背景：抗PD1/PD-L1导向的免疫检查点抑制物(ICI)被广泛用于治疗晚期非小细胞肺癌(NSCLC)。ICI在具有致癌基因改变的非小细胞肺癌中的活性特征很差。我们研究的目的是探讨ICI在致癌成瘾的背景下的疗效。患者和方法：我们对接受ICI单一疗法的晚期非小细胞肺癌患者进行了至少一个致癌驱动因素改变的回顾性研究。匿名数据评估ICI治疗的临床病理特征和结果：最佳反应(RECIST 1.1)、无进展生存率(PFS)和ICI开始后的总生存率(OS)。主要终点是ICI下的PFS。次要终点是最佳反应(RECIST 1.1)和来自ICI启动的OS。结果：我们研究了来自10个国家的24个中心治疗的551名患者。基因突变涉及KRAS(n=271)、EGFR(n=125)、BRAF(n=43)、MET(n=36)、HER2(n=29)、ALK(n=23)、RET(n=16)、ROS1(n=7)和多个驱动因素(n=1)。中位年龄为60岁，性别比为1：1，从不吸烟者/既往吸烟者/现在吸烟者分别为28%/51%/21%，肿瘤以腺癌为主。驾驶员改装的客观有效率分别为：KRAS=26%，BRAF=24%，ROS1=17%，MET=16%，EGFR=12%，HER2=7%，RET=6%，ALK=0%。在整个队列中，中位PFS为2.8个月，OS为13.3个月，最佳应答率为19%。在亚组分析中，EGFR、KRAS、ALK、BRAF、HER2、RET和MET的中位PFS(以月为单位)分别为2.1、3.2、2.5、3.1、2.5、2.1和3.4。在某些亚组中，PFS与PD-L1的表达(KRAS，EGFR)和吸烟状态(BRAF，HER2)呈正相关。结论：ICI诱导了一些具有可操作的驱动因素改变的肿瘤的消退，但临床活性低于KRAS组，ALK组的反应明显缺乏。有可操作的肿瘤改变的患者在考虑将免疫治疗作为单一药物之前，应接受靶向治疗和化疗。
Background: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction.Patients and methods: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation.Results: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2).Conclusions: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.