EGFR-Mutated Squamous Cell Lung Cancer and Its Association With Outcomes.

Abstract

BACKGROUND:

The therapeutic efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced EGFR-mutant lung squamous cell carcinoma (SCC) patients remains uncertain. Furthermore, the factors underlying the responsiveness have not been fully investigated. We therefore investigated the link between genomic profiles and EGFR-TKI efficacy.

MATERIAL AND METHODS:

We consecutively enrolled stage IV, EGFR-mutant, and EGFR-TKI-treated patients with SCC. Patients with EGFR wild-type lung SCC and EGFR-mutant lung adenocarcinoma were consecutively enrolled as controls, and next-generation sequencing (NGS) was performed.

RESULTS:

In total, 28 EGFR-mutant lung SCC, 41 EGFR-mutant lung adenocarcinoma, and 40 EGFR wild-type lung SCC patients were included. Among the patients with EGFR mutations, shorter progression-free survival (PFS) was observed in SCC compared to adenocarcinoma (4.6 vs. 11.0 months, P<0.001). Comparison of the genomic profiles revealed that EGFR-mutant SCC patients had similar mutation characteristics to EGFR-mutant adenocarcinoma patients, but differed from those with EGFR wild-type SCC. Further exploration of EGFR-mutant SCC revealed that mutations in CREBBP (P = 0.005), ZNF217 (P = 0.016), and the Wnt (P = 0.027) pathway were negatively associated with PFS. Mutations in GRM8 (P = 0.025) were associated with improved PFS.

CONCLUSIONS:

EGFR-mutant lung SCC has a worse prognosis than EGFR-mutant adenocarcinoma. Mutations in other genes, such as CREBBP, ZNF217, GRM8, or Wnt that had implications on PFS raise the possibility of understanding mechanisms of resistance to EGFR-TKI in lung SCC, which will aid identification of potential beneficial subgroups of patients with EGFR-mutant SCCs receiving EGFR-TKIs.

• Authors: Rui Jin, Ling Peng, Jiawei Shou, Jin Wang, Yin Jin, Fei Liang, Jing Zhao, Mengmeng Wu, Qin Li, Bin Zhang, Xiaoying Wu, Fen Lan, Lixia Xia, Junrong Yan, Yang Shao, Justin Stebbing, Huahao Shen, Wen Li, Yang Xia
• Journal: Frontiers in oncology (Front Oncol) Vol. 11 Pg. 680804 ( 2021) ISSN: 2234-943X [Print] Switzerland
• PMID: 34195081 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Jin, Peng, Shou, Wang, Jin, Liang, Zhao, Wu, Li, Zhang, Wu, Lan, Xia, Yan, Shao, Stebbing, Shen, Li and Xia.