Lung Adenocarcinoma with Concurrent Exon 19 EGFR Mutation and ALK Rearrangement Responding to Erlotinib

Epidermal growth factor receptor ( EGFR) mutations and anaplastic lymphoma kinase ( ALK) rearrangements are considered mutually exclusive in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LUAC). However, sporadic cases harboring concomitant EGFR and ALK alterations have been increasingly reported. There is no consensus opinion regarding the treatment of patients positive for both molecular alterations. NSCLC with EGFR/ ALK coalterations should be separated into two subtypes: unifocal and multifocal LUAC. Here, we present an overview of the available literature regarding this rare group of patients to provide useful suggestions for therapeutic strategies.

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THE FREQUENCY OF EGFR MUTATION AND ALK REARRANGEMENT IN PATIENTS WITH LUNG ADENOCARCINOMA: THE EXPERIENCE OF A LOCAL HOSPITAL IN TAIWAN

Respirology ◽

10.1111/resp.13420_215 ◽

2018 ◽

Vol 23 ◽

pp. 166-166

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Alk Rearrangement ◽

Local Hospital

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Concomitant EGFR mutation and ALK rearrangement in multifocal lung adenocarcinoma: a case report

Diagnostic Pathology ◽

10.1186/s13000-020-00969-1 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Jun Fan ◽

Junhua Wu ◽

Bo Huang ◽

Yili Zhu ◽

Heshui Shi ◽

...

Keyword(s):

Case Report ◽

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Alk Rearrangement

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Concomitant EGFR Mutation and EML4-ALK Rearrangement in Lung Adenocarcinoma Is More Frequent in Multifocal Lesions

Clinical Lung Cancer ◽

10.1016/j.cllc.2019.04.008 ◽

2019 ◽

Vol 20 (4) ◽

pp. e517-e530 ◽

Cited By ~ 3

Author(s):

Jun Fan ◽

Xiaofang Dai ◽

Zhenkao Wang ◽

Bo Huang ◽

Heshui Shi ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Alk Rearrangement ◽

Multifocal Lesions

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Epidemiology of PD-L1 and ALK expression and EGFR mutational status in Argentinian patients with lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20565 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20565-e20565 ◽

Cited By ~ 1

Author(s):

Ruben Salanova ◽

Julio C Calderazzo Pereyra ◽

Laura Leguina ◽

Asuncion Bena ◽

Mariana Barberis ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Egfr Mutation ◽

Egfr Mutations ◽

Alk Rearrangement ◽

Lung Cancer Patients ◽

Mutational Status ◽

Alk Positive ◽

Egfr Mutant ◽

Exon 19

e20565 Background: Until now, the results of the correlation between PD-L1, ALK expression and EGFR mutations remain controversial. We prospectively evaluated patterns among EGFR mutant, ALK positive and PD-L1 positive lung cancer patients. Methods: PD-L1 and ALK expression was evaluated in 342 adenocarcinomas (AD) of the lung using inmunohistochemestry (anti-PD-L1 22C3, anti-ALK D5F3), and EGFR mutations using real time PCR (therascreen EGFR RGQ PCR Kit version 2). PD-L1 was also evaluated in 36 squamous (SQ) cell carcinomas. Results: 181 of 342 patients with AD were positive for PD-L1. 108 were positive with a TPS value between 1 and 49, and 73 were positive with a TPS value higher than 50 (p = 0.002). 25 of 36 patients with SQ were positive for PD-L1. 17 were positive with a TPS value between 1 and 49, and 8 were positive with a TPS value higher than 50. 133 samples with AD PD-L1 positive and 97 PD-L1 negative were tested for EGFR and ALK, 33 and 14 respectively were positive for EGFR mutations (p = 0.15), with 45% for exon 19 deletions (p = 0.003), 5 and 0 respectively were positive for ALK translocations (p = 0.053). 210 of 342 patients were men and 132 were women, 117 and 64 were positive for PD-L1 expression respectively (p > 0.1). Conclusions: NSCLC with EGFR mutation showed a trend for higher frequency of positive PD-L1 expression and NSCLC harboring ALK rearrangement was significantly associated with PD-L1 expression. These findings might contribute to the understanding of the regulation of PD-L1 expression in lung cancer and its relation to ALK expression and EGFR mutation.

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Co-mutation features in treatment-naïve EGFR-mutant lung adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21616 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21616-e21616

Author(s):

Jun Zhao ◽

Zaiwen Fan ◽

Donghong Chen ◽

Minglei Zhuo ◽

Zhen Liang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Chinese Patients ◽

Therapeutic Effects ◽

Significant Difference ◽

Treatment Naïve ◽

Exon 19 Deletion ◽

Egfr Mutant ◽

Egfr Tkis ◽

Exon 19

e21616 Background: In Chinese patients with lung adenocarcinoma, the positive rate of EGFR mutation was 40% - 50%, EGFR-TKIs therapy for lung cancer was also aimed at this part of patients. However, different EGFR mutation types have different therapeutic effects, this study focuses on different EGFR mutation types to divide the population of lung adenocarcinoma. Methods: We retrospectively reviewed gene test results of two hundred and sixty-two treatment-naïve adenocarcinoma patients. Tumor tissues (199, 76%), plasma (46, 17.5%) and other samples (17, 6.5%) were subject to next-generation sequencing using a 59-gene panel, which enables simultaneously assess SNV, Indel, rearrangements and CNV variations. Results: There were 174 females. These patients were divided into four groups, which 139 were EGFR L858R, 99 were EGFR exon 19 deletion, 7 were EGFR 20 ins and 17 were uncommon EGFR mutations, the co-mutation proportions with EGFR were 84.9% (118/139), 76.8% (76/99), 71.4% (5/7) and 94.1% (16/17) respectively. The mean numbers of co-mutation genes in L858R and exon 19 deletion were 4.173 and 3.258 (p<0.05). TP53 mutation was detected in 14.3% (1/7) 20ins group, which had a significant difference to L858R (59.7%, 83/139) and uncommon mutation groups (70.6%, 12/17) (p<0.05). Meanwhile, EGFR amplification proportion in L858R (18%, 25/139) and exon 19 deletion (6.1%, 6/99) were significantly different (p<0.05). The actionable mutations associated with target therapy involved in multiple pathways, for example, the HRR pathway and cell cycle pathway, related genes had no significant difference among the four groups. In these lung adenocarcinoma patients, we also found 6 EGFR T790M (2.3%, 6/262). Three cases accompanied with exon 19 deletion, and another three were L858R, no distribution in 20ins and uncommon groups. Conclusions: The phenomenon of concurrent gene mutation in treatment-naïve EGFR-mutant lung adenocarcinoma is common. EGFR mutant subgroups have different co-mutation features, like gene number and mutated genes. It may be the factor leading to different therapeutic effects of EGFR-TKIs, and indicate the importance of multiplex molecular test and further researches of target therapies.

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P3.02-043 Clinical and Genetic Features in Lung Adenocarcinoma Without EGFR Mutation and ALK Rearrangement in Taiwan

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2017.09.1572 ◽

2017 ◽

Vol 12 (11) ◽

pp. S2252-S2253

Author(s):

T. Shiao ◽

C. Chiang ◽

Y. Luo ◽

H. Chao ◽

H. Huang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Alk Rearrangement ◽

Genetic Features

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Concomitant EGFR mutation and ALK rearrangement in lung adenocarcinoma is more frequent than expected: Report of a case and review of the literature with demonstration of genes alteration into the same tumor cells

Lung Cancer ◽

10.1016/j.lungcan.2014.09.011 ◽

2014 ◽

Vol 86 (2) ◽

pp. 291-295 ◽

Cited By ~ 38

Author(s):

Licia Baldi ◽

Maria Cecilia Mengoli ◽

Alessandra Bisagni ◽

Maria Chiara Banzi ◽

Corrado Boni ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Tumor Cells ◽

Egfr Mutation ◽

Review Of The Literature ◽

Alk Rearrangement

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Epidermal Growth Factor Receptor ( EGFR ) Mutation in Exon 19 (p.E749Q) Confers Resistance to Gefitinib in One Patient With Lung Adenocarcinoma

Clinical Lung Cancer ◽

10.1016/j.cllc.2017.01.003 ◽

2017 ◽

Vol 18 (3) ◽

pp. e215-e217 ◽

Cited By ~ 2

Author(s):

Giovenzio Genestreti ◽

Dario de Biase ◽

Monica Di Battista ◽

Giovanna Cavallo ◽

Roberta Degli Esposti ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Growth Factor Receptor ◽

Epidermal Growth ◽

Exon 19

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Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) mutations

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.7523 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 7523-7523

Author(s):

Y. Y. Janjigian ◽

B. J. Park ◽

M. G. Kris ◽

V. A. Miller ◽

G. J. Riely ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Disease Free Survival ◽

Stage I ◽

Egfr Mutations ◽

Free Survival ◽

Resected Stage ◽

Lung Adenocarcinomas ◽

Disease Free ◽

Exon 19

7523 Background: Patients with stage IV adenocarcinoma whose tumors harbor EGFR mutations have high rates of response (∼ 75%) and prolonged progression free survival after EGFR tyrosine kinase inhibitor (TKI) treatment. Adjuvant cisplatin-based chemotherapy improves disease free survival (DFS) and overall survival (OS) in patients with resected stages IB-IIIA NSCLC. To see if adjuvant treatment with EGFR TKI (gefitinib or erlotinib) improves DFS in patients with EGFR mutation NSCLC, we conducted a retrospective review of patients with resected lung adenocarcinoma harboring EGFR mutations, some of whom received EGFR TKIs postoperatively. Methods: With Institutional Review Board approval, clinical information was obtained on all patients with stage I-III lung adenocarcinoma harboring EGFR exon 19 or 21 mutations that underwent resection at MSKCC between May 2002 and August 2008. Age, gender, type of surgery, histology, EGFR mutation status (exon 19 deletions and exon 21 L858R), stage, perioperative therapy and survival were recorded. Kaplan-Meier analysis and Cox regression analysis were performed. Results: We studied 150 patients (112 women, 38 men) with completely resected stage I-III lung adenocarcinoma whose resection specimens contained EGFR activating mutations in exon 19 or 21. Median age was 69. Forty two patients (28%) received cytotoxic chemotherapy. Forty eight (32%) received either erlotinib (n=26) or gefitinib (n=22) postoperatively. The median time on TKI was 16 months. The median DFS was 43 months in the group that received a TKI vs. 31 months for those that did not. After controlling for stage, individuals who received adjuvant gefitinib or erlotinib had a better DFS (HR=0.38, 95%CI: 0.16–0.90) than the non-TKI group (p=0.03). The median overall survival has not been reached. Conclusions: These data indicate that the adjuvant use of either gefitinib or erlotinib improves DFS in patients with completely resected stage I -III lung adenocarcinomas with mutations in EGFR exons 19 and 21. These data justify a randomized trial in similar patients. [Table: see text]

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