与BIM缺失多态性相比，伴随的基因改变对EGFR突变的晚期非小细胞肺癌中EGFR-TKIs的临床获益影响更大。
Concomitant genetic alterations having greater impact on the clinical benefit of EGFR-TKIs in EGFR-mutant advanced NSCLC than BIM deletion polymorphism.
作者信息
Liu Si-Yang, Zhou Jia-Ying, Li Wen-Feng, Sun Hao, Zhang Yi-Chen, Yan Hong-Hong, Chen Zhi-Hong, Chen Chun-Xiang, Ye Jun-Yi, Yang Jin-Ji, Zhou Qing, Zhang Xu-Chao, Wu Yi-Long
机构信息
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, 510080, China.
Burning Rock Biotech, Guangzhou, 510000, China.
出版信息
Clin Transl Med. 2020 Jan;10(1):337-345. doi: 10.1002/ctm2.12.
BACKGROUND
In previous studies, the predictive role of BIM deletion polymorphism with respect to responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been controversial. The potential reasons for these inconsistent findings were unknown.
METHODS
Data from CTONG0901 clinical trial and medical records of Guangdong Lung Cancer Institute (GLCI) were retrospectively pooled. A total of 194 and 141 EGFR-mutant non-small cell lung cancer (NSCLC) patients treated with first- and second-generation EGFR-TKIs were examined in the CTONG0901 and GLCI cohorts, respectively. Sixty-eight patients were treated with third-generation EGFR-TKIs in the GLCI cohort. The BIM gene status was examined by next-generation sequencing.
RESULTS
The frequency of BIM deletion polymorphism was 11.3% and 17.0% in CTONG0901 and GLCI cohorts, respectively. For first- and second-generation EGFR-TKIs in CTONG0901 cohort, objective response (ORR) was 54.5% in BIM deletion group versus 56.4% in wild-type BIM group (P = .87); disease control rate (DCR) was 90.9% versus 88.4% (P = 1.00); progression-free survival (PFS) was 10.5 versus 11.2 months (P = .59); and overall survival (OS) was 20.5 versus 20.5 months (P = .73). In GLCI cohort, ORR was 54.2% versus 60.7% (P = .55); DCR was 91.7% versus 96.6% (P = .27); PFS was 10.1 versus 11.6 months (P = .63); and OS was 58.5 versus 45.0 months (P = .93). For third-generation EGFR-TKIs, ORR was 18.2% versus 63.2% (P = .02); DCR was 81.8% versus 96.5%, (P = .12); PFS was 5.8 versus 9.0 months (P = .13); and OS was 30.0 versus 24.8 months (P = .85). Cox regression analysis showed that concomitant genetic alterations could adversely affect the response to EGFR-TKIs, but not BIM deletion.
CONCLUSIONS
The presence of BIM deletion showed no relation to an impaired response to first-, second-, and third-generation EGFR-TKIs in NSCLC patients. The factors influencing the response of EGFR-TKIs were concomitant genetic alterations, but not BIM deletion.
背景
在先前的研究中，BIM缺失多态性对表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）反应的预测作用一直存在争议。这些不一致结果的潜在原因尚不清楚。
方法
回顾性汇总CTONG0901临床试验数据和广东省肺癌研究所（GLCI）的病历。CTONG0901队列和GLCI队列中分别有194例和141例接受第一代和第二代EGFR-TKIs治疗的EGFR突变非小细胞肺癌（NSCLC）患者接受了检查。GLCI队列中有68例患者接受了第三代EGFR-TKIs治疗。通过下一代测序检测BIM基因状态。
结果
CTONG0901队列和GLCI队列中BIM缺失多态性的频率分别为11.3%和17.0%。对于CTONG0901队列中的第一代和第二代EGFR-TKIs，BIM缺失组的客观缓解率（ORR）为54.5%，野生型BIM组为56.4%（P = 0.87）；疾病控制率（DCR）为90.9%对88.4%（P = 1.00）；无进展生存期（PFS）为10.5个月对11.2个月（P = 0.59）；总生存期（OS）为20.5个月对20.5个月（P = 0.73）。在GLCI队列中，ORR为54.2%对60.7%（P = 0.55）；DCR为91.7%对96.6%（P = 0.27）；PFS为10.1个月对11.6个月（P = 0.63）；OS为58.5个月对45.0个月（P = 0.93）。对于第三代EGFR-TKIs，ORR为18.2%对63.2%（P = 0.02）；DCR为81.8%对96.5%（P = 0.12）；PFS为5.8个月对9.0个月（P = 0.13）；OS为30.0个月对24.8个月（P = 0.85）。Cox回归分析表明，伴随的基因改变可能会对EGFR-TKIs的反应产生不利影响，但BIM缺失不会。
结论
BIM缺失的存在与NSCLC患者对第一代、第二代和第三代EGFR-TKIs反应受损无关。影响EGFR-TKIs反应的因素是伴随的基因改变，而不是BIM缺失。
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