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Lung Cancer. 2020 Jan;139:133-139. doi: 10.1016/j.lungcan.2019.11.018. Epub 2019 Nov 24.

Uncommon EGFR mutations associate with lower incidence of T790M mutation after EGFR-TKI treatment in patients with advanced NSCLC.

Yang S1, Mao S2, Li X3, Zhao C4, Liu Q5, Yu X6, Wang Y7, Liu Y8, Pan Y9, Wang C10, Gao G11, Li W12, Xiong A13, Chen B14, Sun H15, He Y16, Wu F17, Chen X18, Su C19, Ren S20, Zhou C21.

Author information

1
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: syang0213@foxmail.com.
2
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: maosq17@163.com.
3
Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: bug_lily2003@163.com.
4
Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: dlyzcr-zc@163.com.
5
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: 991154839@qq.com.
6
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: 980860214@qq.com.
7
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: 1259347283@qq.com.
8
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: yiwei-liu@qq.com.
9
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: lovepanyy@163.com.
10
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: 695868798@163.com.
11
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: ghgao103@hotmail.com.
12
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: leewluck@foxmail.com.
13
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: anwenxiong@yeah.net.
14
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: binchen629@126.com.
15
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: sunhui2018@163.com.
16
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: 2250601@qq.com.
17
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: fywu@163.com.
18
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: cheetos_xx@126.com.
19
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: susu_mail@126.com.
20
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: harry_ren@126.com.
21
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: caicunzhoudr@qq.com.

Abstract

OBJECTIVES:

Advanced non-small cell lung cancer (NSCLC) patients harboring non-resistant uncommon epidermal growth factor receptor (EGFR) mutations have stepped into the era of targeted therapy. This study aimed to investigate the incidence of acquired T790M mutation and their outcome to subsequent osimertinib in patients of advanced NSCLC harboring uncommon EGFR mutations.

PATIENTS AND METHODS:

Patients with EGFR mutation and performed re-biopsy after progression on prior EGFR-tyrosine kinase inhibitors (TKIs) were reviewed and analyzed. Those with T790M mutation and received subsequent osimertinib treatment were further collected for survival analysis.

RESULTS:

Finally, 754 patients, including 48 with uncommon mutation, 362 with 19del and 344 with L858R were enrolled. T790M mutation was identified in 341 patients (341/754, 45.2 %). The incidence of T790M mutation was 27.1 % in patients harboring uncommon mutations, significantly lower than 55.2 % and 37.2 % of 19del and L858R (p < 0.001). Logistic regression analysis further found uncommon mutation associated with significantly lower probability of developing T790M (odds ratio [OR] = 0.32, 95 % confidence interval [CI] 0.16-0.64). Among 236 patients received subsequent osimertinib treatment (including 12 uncommon mutation, 145 19del and 79 L858R), patients harboring uncommon mutations showed significantly shorter progression free survival (PFS) (median: 4.6 vs. 11.6 vs. 12.1 months, p < 0.001) and overall survival (OS) (median: 8.1 vs. 35.4 vs. 24.9 months, p = 0.001) compared with 19del and L858R, also associated with numerically lower objective response rate (ORR) (p = 0.085) and lower disease control rate (DCR) (p = 0.074). Multivariate analysis further found that uncommon mutation was the only one significantly associated with both PFS (hazard ratio [HR] = 3.44, 95 %CI 1.79-6.58) and OS (HR = 3.64, 95 %CI 1.66-7.99).

CONCLUSIONS:

Uncommon EGFR mutation showed a significantly lower incidence of acquired T790M mutation and benefited significantly less from subsequent osimertinib treatment than common EGFR mutations in patients with advanced NSCLC.

KEYWORDS:

Acquired T790M mutation; Non-small cell lung cancer; Osimertinib; Uncommon EGFR mutation

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