已发表论文

中国肺癌患者 ERBB2  外显子 20 插入的临床特征和对阿法替尼的反应异质性

 

Authors Liu Z, Wu L, Cao J, Yang Z, Zhou C, Cao L, Wu H, Shen H, Jin M, Zhang Y, Mao X, Xiang J, Ma K, Li B, Zhang T, Hu Y

Received 7 May 2018

Accepted for publication 7 August 2018

Published 23 October 2018 Volume 2018:11 Pages 7323—7331

DOI https://doi.org/10.2147/OTT.S173391

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Dr Tohru Yamada

Purpose: ERBB2  exon 20 insertions (20ins) have been identified as oncogenic drivers in lung cancers. Lung cancer patients with 20ins benefit from afatinib. However, response heterogeneity was observed in patients harboring different 20ins subtypes. In this study, we interrogated clinical characteristics in ERBB2 -mutated Chinese lung cancer and investigated the clinical outcomes of specific ERBB2  20ins in response to afatinib.
Experimental design: In this study, we retrospectively collected genomic profiling data of 7,520 lung cancer patients sequenced using next-generation sequencing in a Clinical Laboratory Improvement Amendments-certified laboratory. We analyzed the clinical and molecular features of patients harboring ERBB2  20ins and evaluated clinical outcomes of 19 patients with clinical records after afatinib treatment.
Results: ERBB2  20ins were identified in 2.27% (171/7,520) of this lung cancer cohort. It occurred with a high proportion in females with adenocarcinoma histology. ERBB2  20ins was mutually exclusive with other well-established lung cancer oncogenic driver mutations. The most frequently appearing subtype was Y772_A775dup (69.6%) and several novel insertion subtypes were also identified. The correlations of specific 20ins subtypes and survival were investigated. The presence of a glycine at position 778 in ERBB2  was suggested to be a common feature of drug sensitivity mutations. Patients harboring G778_P780dup (G778) subtype achieved longer median progression-free survival and median overall survival than other 20ins (non-G778) subtypes (median progression-free survival, 10 vs 3.3 months, =0.32; median overall survival, 19.7 vs 7 months, =0.16). Moreover, we presented the first clinical case of a lung squamous cell carcinoma patient harboring ERBB2  20ins who achieved partial response to afatinib.
Conclusion: This study interrogated the characteristics of ERBB2  20ins in a large cohort from single ethnicity and demonstrated the response heterogeneity to afatinib among different ERBB2  20ins subtypes. Further studies in a larger cohort are needed to investigate the underlying molecular mechanisms and clinical response of different ERBB2  20ins subtypes.
Keywords: ERBB2 , lung cancer, afatinib, survival, heterogeneity




Figure 5 A lung SCC patient was identified as harboring ERBB2 20ins and responded to afatinib.