Distinct Benefit of Overall Survival between Patients with Non-Small-Cell Lung Cancer Harboring EGFR Exon 19 Deletion and Exon 21 L858R Substitution

Chemotherapy ◽  
2017 ◽  
Vol 62 (3) ◽  
pp. 151-158 ◽  
Author(s):  
Nobuyuki Koyama ◽  
Yasutaka Watanabe ◽  
Yuki Iwai ◽  
Rumi Kawamura ◽  
Chihiro Miwa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Multivariate Analyses ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 19 Deletion ◽  
Exon 19

Background: Exon 19 deletion (Del19) and exon 21 L858R substitution (L858R), which account for 90% of epidermal growth factor receptor (EGFR) mutations as common mutations, are associated with favorable outcomes with EGFR-tyrosine kinase inhibitors (TKIs) compared with other uncommon EGFR mutations in non-small-cell lung cancer (NSCLC). However, whether there are differences in overall survival (OS) between patients with these common EGFR mutations remains controversial. Methods: The subjects studied were 74 NSCLC patients with common EGFR mutations treated with gefitinib or erlotinib. Using univariate and multivariate analyses, we retrospectively compared the clinicopahological characteristics of patients harboring Del19 with those harboring L858R. Results: Compared with patients harboring L858R, EGFR-TKIs provided a significant OS benefit in patients harboring Del19 (p = 0.024), as well as favorable therapeutic responses (p = 0.045) and progression-free survival (PFS) benefits (p = 0.031). In multivariate analyses, Del19 was independently associated with PFS (p = 0.029) and OS (p = 0.009), whereas no parameters other than pleural dissemination at the initial treatment were associated with EGFR mutation types. Conclusion: Del19 and L858R have distinct prognostic implications and may require individual therapeutic strategies.

Metastatic brain tumors from non-small cell lung cancer with EGFR mutations: Distinguishing influence of exon 19 deletion on radiographic features

Lung Cancer ◽  
2012 ◽  
Vol 77 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Akimasa Sekine ◽  
Terufumi Kato ◽  
Eri Hagiwara ◽  
Takeshi Shinohara ◽  
Takanobu Komagata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Tumors ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Metastatic Brain Tumors ◽  
Small Cell Lung ◽  
Exon 19 Deletion ◽  
Exon 19

scholarly journals Histological transformation of lung adenocarcinoma to small cell lung cancer with mutant C797S conferring acquired resistance to osimertinib

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052092791 ◽  
Author(s):  
Xiaohui Ren ◽  
Xinfeng Cai ◽  
Jing Li ◽  
Xia Zhang ◽  
Jianfei Yu ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Exon 19 Deletion ◽  
Exon 19

Epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer may initially respond to EGFR tyrosine kinase inhibitors (TKIs), but may subsequently become resistant; however, the resistance mechanisms remain unclear. We report a rare case of acquired resistance to osimertinib associated with transformation to small cell lung cancer (SCLC) with cis-C797S mutation. A man with recurrent lung adenocarcinoma harboring an EGFR exon 19 deletion received erlotinib for 10 months following curative surgery and adjuvant chemotherapy. However, he switched to osimertinib after repeat biopsy showed EGFR exon 19 deletion and T790M mutation leading to erlotinib resistance. His disease progressed after 15 months and repeat biopsy showed SCLC. Next-generation sequencing of peripheral blood detected EGFR exon 19 deletion, T790M mutation, cis-C797S mutation, and RB1 inactivation. The tumor was reduced after four cycles of etoposide and cisplatin and his respiratory symptoms improved. However, computed tomography after six cycles of chemotherapy showed multiple bilateral lung lesions, and single-photon emission computed tomography showed bone metastasis. The patient received paclitaxel plus cisplatin for two cycles with partial response. Because heterogeneous genetic and phenotypic mechanisms of TKI-resistance may occur at different times and locations, histopathological and molecular testing both provide evidence to support appropriate treatment.

scholarly journals The impact of EGFR exon 19 deletion subtypes on clinical outcomes in non-small cell lung cancer

2020 ◽  
Vol 9 (4) ◽  
pp. 1149-1158
Author(s):  
Chao Zhao ◽  
Tao Jiang ◽  
Jiayu Li ◽  
Yan Wang ◽  
Chunxia Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Exon 19 Deletion ◽  
The Impact ◽  
Exon 19

Survival benefit of gefitinib treated non-small-cell lung cancer patients with exon 19 deletion mutations in epidermal growth factor receptor (EGFR), detected by a new sensitive PCR-based method

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10614-10614
Author(s):  
E. Nakajima ◽  
M. Sugita ◽  
R. Dziadziuszko ◽  
M. Tsuboi ◽  
H. Kato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survival Benefit ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Deletion Mutations ◽  
Exon 19 Deletion ◽  
Exon 19

10614 Background: As for two common types of EGFR mutations, patients with exon 19 deletion mutations have longer survival than those with the L858R point mutations in exon 21 after treatment with EGFR inhibitors. We have developed a simple, polymerase chain reaction (PCR)-based method to detect exon 19 deletion mutations, and evaluated survival benefit of gefitinib treated patients with exon 19 deletion mutations versus patients without these mutations. Patients and methods: Tumor tissue was microdissected under stereoscopic microscopy from formalin-fixed paraffin-embedded sections, and DNA was extracted from tumor cells with DNeasy (Qiagen). Our method consisted of two different semi-nested PCRs with the deletion screening PCR and the common deletion specific PCR. All of the known deletions present in cell lines were detected by this method without direct sequencing. The result was validated by sequencing of exon 19. 73 non-small-cell lung cancer (NSCLC) Japanese patients treated with gefitinib were analyzed with this method. Study group consisted of 28 females (38%), 29 never smokers (40%) and 57 patients with adenocarcinoma (78%). Results: The PCR-based method detected mutations at mutant to wild type DNA copy ratio of 1/600, and in samples as small as 30 ng of purified DNA. Exon 19 deletion mutations were found in 25 (34%) patients. This method was more sensitive than conventional sequencing. The sequencing was performed in 19 patients with mutations and could not detect 3 deletions. Among 60 assessable patients 14 had overall response (23%). Objective response rates to gefitinib were observed in 7/21 patients with exon 19 deletion mutations (33%), and 7/39 patients without exon 19 deletion mutations (17%) (P = .211). Patients with exon 19 deletion mutations survived significantly longer than those without exon 19 deletion mutations (P = .017). Conclusions: The PCR-based method to detect exon 19 deletion mutations is cost effective and very sensitive, compared to previously described methods. We demonstrated survival benefit in NSCLC patients with exon 19 deletion mutations treated with gefitinib, and our PCR-based method is easily applicable for clinical use. No significant financial relationships to disclose.

scholarly journals Complete Resolution of Sellar Metastasis in a Patient With NSCLC Treated With Osimertinib

2019 ◽  
Vol 3 (10) ◽  
pp. 1887-1891
Author(s):  
WuQiang Fan ◽  
Jason Sloane ◽  
Lisa B Nachtigall
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Complete Resolution ◽  
Small Cell ◽  
Deletion Mutation ◽  
Illustrative Case ◽  
Small Cell Lung ◽  
Exon 19 Deletion ◽  
Exon 19

Abstract Non–small cell lung cancer with pituitary metastasis (NSCLC-PM) is a devastating disease; however, treatment is being revolutionized by a novel therapy targeting highly specific tumor signals, such as the mutation of epidermal growth factor receptors (EGFRs). Long-term management of hormonal defects in this population has become a unique neuroendocrine clinical challenge. We report the case of a 73-year-old female nonsmoker who was diagnosed with stage IV non–small cell lung cancer. The initial staging evaluation revealed a 7 × 11 × 21-mm sellar lesion abutting the optic chiasm and causing clinical hypopituitarism. The patient received three cycles of chemotherapy with carboplatin and pemetrexed, which was discontinued because of major cumulative side effects of myelosuppression and kidney disease. Eight months later, scans demonstrated evidence of disease progression. A repeated lung nodule biopsy revealed an EGFR exon 19 deletion mutation. EGFR-targeted therapy with osimertinib 80 mg daily was initiated. A complete resolution of the pituitary lesion was evident on a follow-up pituitary MRI 5 weeks later and was sustained 1 year after. However, the panhypopituitarism persisted. This is an illustrative case of NSCLC-PM with EGFR exon 19 deletion mutation, wherein osimertinib, a third-generation EGFR‒tyrosine kinase inhibitor, eradicated the sellar metastasis and prevented the need for radiotherapy. However, the neuroendocrine deficits persisted despite anatomic improvement.

ERCC1 expression by immunohistochemistry and EGFR mutations in resected non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7646-7646 ◽  
Author(s):  
K. Lee ◽  
S. Han ◽  
H. Min ◽  
D. Oh ◽  
S. Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Excision Repair ◽  
Direct Sequencing ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Ercc1 Expression

7646 Background: To investigate whether excision repair cross-complementation group 1 (ERCC1) expression, as determined immunohistochemically, and mutations of epidermal growth factor receptor (EGFR) are related to the prognosis of curatively resected non-small cell lung cancer (NSCLC), and whether these two markers are related. Methods: One-hundred and thirty-three consecutive patients with NSCLC who did not receive adjuvant chemotherapy after curative surgery were included in this study. Representative areas from formalin-fixed paraffin-embedded tumor samples were chosen for tissue microarray analysis. Immunohistochemistry was performed for ERCC1 and the median semiquantitative H-score was used as a cut-off. EGFR mutations (exons 18, 19, and 21) were analyzed by the direct sequencing of tumor samples. Results: ERCC1 expression was evaluable in 130 patients and ERCC1 was found to be positive in 80 patients (61.5%). Moreover, ERCC1 was expressed more frequently in smokers and in squamous cell carcinomas. Patients with positive ERCC1 expression survived longer (median overall survival 2,742 days for ERCC1-positive vs. 1,423 days for ERCC1-negative, P=.0463). EGFR mutations were found in 27 patients (20.3%) but they were not found to affect overall survival. Interestingly, EGFR mutations were more frequent in ERCC1-negative tumors (12.5% in ERCC1-positive vs. 30% in ERCC1-negative tumors, P=0.014). Conclusions: ERCC1 expression was identified as a prognostic marker of longer survival in resected NSCLCs. In addition, EGFR mutations were more frequently found in ERCC1-negative tumors, but were not found to affect survival in our patient group. No significant financial relationships to disclose.

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