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 Table of Contents  
CORRESPONDENCE
Year : 2018  |  Volume : 131  |  Issue : 8  |  Page : 1005-1006

Clinical Analysis of Uncommon Epidermal Growth Factor Receptor Mutations in 16 Cases of Nonsmall Cell Lung Cancer


1 Department of Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China
2 Department of Thoracic Surgery, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China
3 Department of Pathology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China

Date of Submission09-Oct-2017
Date of Web Publication12-Apr-2018

Correspondence Address:
Dr. Qun-Hui Wang
Department of Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0366-6999.229887

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How to cite this article:
Hu AM, Li YS, Zhao D, Hu FB, Wang QH, Li BL. Clinical Analysis of Uncommon Epidermal Growth Factor Receptor Mutations in 16 Cases of Nonsmall Cell Lung Cancer. Chin Med J 2018;131:1005-6

How to cite this URL:
Hu AM, Li YS, Zhao D, Hu FB, Wang QH, Li BL. Clinical Analysis of Uncommon Epidermal Growth Factor Receptor Mutations in 16 Cases of Nonsmall Cell Lung Cancer. Chin Med J [serial online] 2018 [cited 2018 Jul 18];131:1005-6. Available from: http://www.cmj.org/text.asp?2018/131/8/1005/229887



To the Editor: Epidermal growth factor receptor (EGFR) is overexpressed in non-small cell lung cancer (NSCLC) and contains a tyrosine kinase inhibitor (TKI) domain which acts as an important therapeutic target. Previous studies have observed the efficacy of EGFR-TKIs in the most commonly targeted exon mutations (19 and 21). This study was to investigat the pathologic features of uncommon EGFR mutations and the clinical efficacies of EGFR-TKIs treatment.

A retrospective analysis was performed for 16 NSCLC patients with uncommon EGFR mutations who were first treated at Beijing Chest Hospital from December 2011 to December 2014. All patients were diagnosed as NSCLC by pathological and immunohistochemistry examinations. Moreover, all the patients were at IIIb/IV stage or in advanced stages with postoperative recurrence. Before treatment, all the patients were screened for EGFR mutation in the tissue specimens by polymerase chain reaction-Sanger sequencing method and considered as positive EGFR mutations. Computed tomography examination was performed after 1 month of EGFR-TKIs treatment. Efficacy evaluation was performed according to the Response Evaluation Criteria in Solid Tumors.

Progression-free survival (PFS) and overall survival (OS) were observed. Follow-up was performed using telephone and household registration system at least every 2 months. The last follow-up occurred on May 1, 2016.

Patients ranged from 45 to 82 years old (with a median age of 58.5 years). They were commonly observed in women (10/16, 62.5%), nonsmokers (11/16, 68.8%), and adenocarcinoma (15/16, 93.8%). In 16 cases, seven cases were observed in exon 21, three cases in exon 20, four cases in exon 18, one case in exons 20 and 21 together, as well as one case in exons 18 and 20 together. All were mainly point mutations and embedded mutations, without any deletion mutations.

A total of 12 types were found. In exon 21, six mutation types were all point mutations, and mainly was L861Q. In exon 18, three mutation types were all point mutations and mainly G719C/A mutation was observed (3/5, 60%). In exon 20, three types were found, one type for embedded mutations and other two types for point mutations.

Seven of the 16 cases underwent targeted therapy. The median PFS was 6.0 months (range: 1.3–26.0 months), and median OS was 30.3 months (range: 7.4–64.0 months). In three cases of exon 21 mutations, one case had P848L mutations for erlotinib, and the longest PFS of 26 months was observed. In exon 18 mutation, one case had G719C mutations for Erlotinib with PFS of 18 months. In three cases of exon 20 mutations, the longest PFS was 2 months [Table 1].
Table 1: Pathological features and clinical efficacy of 16 cases of uncommon EGFR mutations

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According to the previous studies, the EGFR-TKIs treatment showed a median PFS of 6 months, which was lower than the sensitive mutations whose first-line PFS was between 9 and 14 months, but higher than the wild type whose first-line PFS was about 1 month.[1],[2] In our study, the most frequent uncommon mutations were G719 (3/16) in exon 18 and L861 (3/16) in exon 21. PFS of patient with G719 by erlotinib treatment was 18 months, while L861Q by gefitinib treatment was 6 months. PFS of G719 for the first-generation TKI was significantly better than L861 mutations. One patient with insertion mutations of exon 20 treated with first-generation EGFR-TKIs showed a PFS of 1.5 months. We first found two uncommon mutations in exon 20, which were T785I and R776G administered with oral icotinib and erlotinib, respectively. PFS were 2.0 and 1.3 months, respectively, suggesting that they were resistant to the first-generation EGFR-TKIs.

L858R and E866Q double mutations in exon 21 were other uncommon mutations. The patient was given gefitinib and icotinib orally, and showed a PFS of 7.3 months that was close to the sensitive mutations, for it may be associated with L858R-sensitive mutations. In addition, one case of uncommon mutation P848L in exon 21 was given erlotinib, whose PFS was 26 months, similar to sensitive mutations. The specimen of this case was obtained by bronchoscopy and it may contain components of sensitive mutations.

In 16 cases, 13 cases underwent chemotherapy, of which 5 cases had local radiotherapy due to the progression of local lesion. The median OS of the 13 cases was 35 months; however, median OS of the other 3 cases was 8.8 months. Therefore, this study believed that the prolonged OS was impacted largely by chemoradiotherapy, because it can clear some clones that were resistant to EGFR-TKIs and directly kill the tumor cells.

In summary, PFS of the uncommon mutations in this study mostly were lower than the classical mutations, but higher than the EGFR wild types. Moreover, patients obtained survival benefits from the targeted therapy, and the longest PFS was up to 26 months. Chemoradiotherapy can still be a reasonable choice as first-line therapy in the better physical condition. Due to less clinical data and controversial results, there is no definite conclusion on how to treat patients with uncommon mutations, and it still needs to be further studied by large-scale clinical data, in vitro experiments, and testing tools of EGFR-TKIs sensitivity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009;361:958-67. doi: 10.1056/NEJMoa0904554.  Back to cited text no. 1
[PUBMED]    
2.
Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011;12:735-42. doi: 10.1016/S1470-2045(11)70184-X.  Back to cited text no. 2
[PUBMED]    



 
 
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