Impact of HER2 expression on EGFR-TKI treatment outcomes in lung tumors harboring EGFR mutations: A HER2-CS study subset analysis

被引：8

作者：

Ohashi, Kadoaki ^{[1
]}

Ninomiya, Kiichiro ^{[1
]}

Yoshioka, Hiroshige ^{[2
,20
]}

Bessho, Akihiro ^{[3
]}

Shibayama, Takuo ^{[4
]}

Aoe, Keisuke ^{[5
]}

Ishikawa, Nobuhisa ^{[6
]}

Kozuki, Toshiyuki ^{[7
]}

Kawai, Haruyuki ^{[8
]}

Kuyama, Shoichi ^{[9
]}

Miyoshi, Seigo ^{[10
]}

Fujitaka, Kazunori ^{[11
]}

Obata, Hideto ^{[12
]}

Tsubata, Yukari ^{[13
]}

Awaya, Yoshikazu ^{[14
]}

Inoue, Masaaki ^{[15
]}

Inoue, Koji ^{[16
]}

Horita, Naokatsu ^{[17
]}

Yanai, Hiroyuki ^{[18
]}

Hotta, Katsuyuki ^{[19
]}

Kiura, Katsuyuki ^{[1
]}

机构：

[1] Okayama Univ Hosp, Dept Resp Med, Okayama, Japan

[2] Kurashiki Cent Hosp, Dept Resp Med, Kurashiki, Okayama, Japan

[3] Japanese Red Cross Okayama Hosp, Dept Resp Med, Okayama, Japan

[4] Natl Hosp Org, Dept Resp Med, Okayama Med Ctr, Okayama, Japan

[5] Natl Hosp Org, Dept Med Oncol, Yamaguchi Ube Med Ctr, Ube, Yamaguchi, Japan

[6] Hiroshima Prefectural Hosp, Dept Resp Med, Hiroshima, Japan

[7] Natl Hosp Org, Shikoku Canc Ctr, Dept Thorac Oncol & Med, Shikoku, Ehime, Japan

[8] Okayama Saiseikai Gen Hosp, Dept Internal Med, Okayama, Japan

[9] Iwakuni Med Ctr, Dept Resp Med, Iwakuni, Japan

[10] Ehime Univ, Grad Sch Med, Dept Cardiol Pulmonol Hypertens & Nephrol, Matsuyama, Ehime, Japan

[11] Hiroshima Univ Hosp, Dept Resp Med, Hiroshima, Japan

[12] Yamaguchi Ken Saiseikai Shimonoseki Gen Hosp, Dept Resp Med, Shimonoseki, Yamaguchi, Japan

[13] Shimane Univ, Fac Med, Div Med Oncol & Resp Med, Dept Internal Med, Matsue, Shimane, Japan

[14] Miyoshi Cent Hosp, Dept Resp Med, Saitama, Japan

[15] Shimonoseki City Hosp, Dept Chest Surg, Shimonoseki, Yamaguchi, Japan

[16] Ehime Prefectural Cent Hosp, Dept Resp Med, Matsuyama, Ehime, Japan

[17] Kure Kyosai Hosp, Dept Resp Med, Kure, Hiroshima, Japan

[18] Okayama Univ Hosp, Dept Pathol, Okayama, Japan

[19] Okayama Univ Hosp, Ctr Innovat Clin Med, 2-5-1 Shikata Cho Kita Ward, Okayama 7008558, Japan

[20] Kansai Med Univ Hosp, Dept Thorac Oncol, Hirakata, Osaka, Japan

来源：

LUNG CANCER | 2020年 / 150卷

关键词：

Epidermal growth factor receptor mutations; Performance status; Human epidermal growth factor receptor-2; Time-To-Treatment failure; GROWTH-FACTOR RECEPTOR; ACQUIRED-RESISTANCE; TRASTUZUMAB EMTANSINE; GENE-MUTATIONS; PHASE-II; CANCER; MUTANT; AMPLIFICATION; OVEREXPRESSION; ADENOCARCINOMA;

D O I：

10.1016/j.lungcan.2020.09.024

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Objectives: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatment for EGFR-mutated non-small-cell lung carcinoma (NSCLC); however, a biomarker to predict their efficacy has not been established. Although human epidermal growth factor receptor-2 (HER2) aberrations constitute a potential mechanism for acquired resistance to EGFR-TKIs, the impact of HER2 on EGFR-TKI treatment outcomes has not been systematically evaluated. In this post-hoc subgroup study, we examined the impact of HER2 on the effect of EGFR-TKIs in patients with NSCLC harboring EGFR mutations. Materials and Methods: Of 1126 patients with NSCLC enrolled into a prospective cohort study (HER2-CS study), we analyzed data of 356 (32 %) patients with EGFR-mutant tumors. HER2 protein expression levels were determined by immunohistochemistry (IHC) with the gastric cancer criteria. Patients were divided either to an HER2-P group (HER2-IHC2+/3+) or an HER2-N group (HER2-IHC0/1+). We primarily assessed differences in the time-to-treatment failure (TTF) of EGFR-TKI between the groups. Results: The HER2 scoring was as follows: IHC0 (n = 76, 21 %), IHC1+ (n = 199, 56 %), IHC2+ (n = 72, 20 %), and IHC3+ (n = 9, 3 %). The patients' demographics were similar in the HER2-P and HER2-N groups. The HER2-P group showed a significantly shorter EGFR-TKI TTF than the HER2-N group (hazard ratio [HR]: 1.657, 95 % confidence interval [CI]: 1.076-2.552; median: 13.3 vs. 19.1 months). The magnitude of the negative impact of TTF was especially dependent on performance status (PS). HER2 expression significantly deteriorated the TTF in the subgroup with PS 2 (HR: 5.497, 95 % CI: 1.510-20.02), but not in that with better PS (HR: 1.437, 95 % CI: 0.899-2.298) (pinteraction = 0.015). Conclusion: In the current cohort, HER2 protein expression in EGFR-mutant NSCLC may have a negative impact on the effect of EGFR-TKIs, the effect of which was PS dependent.

引用

页码：83 / 89

页数：7

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