NSCLC Patients Harbouring Rare or Complex EGFR Mutations Are More Often Smokers and Might Not Benefit from First-Line Tyrosine Kinase Inhibitor Therapy

Kauffmann-Guerrero, Diego; Huber, Rudolf M.; Reu, Simone; Tufman, Amanda; Mertsch, Pontus; Syunyaeva, Zulfiya; Jung, Andreas; Kahnert, Kathrin

doi:10.1159/000484175

Cited by 16 publications

(17 citation statements)

References 21 publications

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“…Within our cohort, there was a trend toward more frequent uncommon EGFR mutations among ES patients, although statistically not significant, which is consistent with other Asian studies 4,31. On the other hand, a significant association of EGFR uncommon mutations with smoking has been described amongst European lung cancer patients 32…”

Section: Discussionsupporting

confidence: 91%

Impact of smoking on frequency and spectrum of K-RAS and EGFR mutations in treatment naive Indonesian lung cancer patients

Masykura

Zaini²,

Syahruddin³

et al. 2019

LCTT

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Background: Indonesia has the highest cigarette consumption in the world. We explored the clinical impact of smoking on the prevalence of EGFR and K-RAS mutations and survival in this prospective study. Methods: 143 treatment naive lung cancer patients were recruited from Persahabatan Hospital, a national tertiary hospital. DNA from cytological specimens had been extracted and genotyped for both EGFR and K-RAS mutations using a combination of PCR high resolution melting, restriction fragment length polymorphism (RFLP) and direct DNA sequencing. Results: EGFR mutation frequency in never smokers (NS) and ever smokers (ES) were 75% and 56% ( p = 0.0401), respectively. In this cohort, the overall K-RAS mutation rate was 7%. Neither gender nor smoking history were associated with K-RAS mutation significantly. However, K-RAS transversion mutations were more common in male ES than transition mutations. Smoking history did not affect EGFR and K-RAS mutation frequencies in women. Concurrent EGFR / K-RAS mutation rate was 2.8% (4 of 143 patients). Four out of 91 EGFR mutation positive patients (4.4%) had simultaneous K-RAS mutation. Conclusions: In region where cigarette consumption is prevalent, smoking history affected frequencies of EGFR and K-RAS mutations, mainly in males.

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Section: Discussionsupporting

confidence: 91%

Impact of smoking on frequency and spectrum of K-RAS and EGFR mutations in treatment naive Indonesian lung cancer patients

Masykura

Zaini²,

Syahruddin³

et al. 2019

LCTT

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“…In this study, 3.3% of cases with rare-type EGFR mutations were not detected using PCR. Rare EGFR mutations had been reported to be observed in male smokers with inferior EGFR TKI response [13,14]. However, recent studies have reported that rare EGFR mutations can be more effectively targetable with appropriate TKIs [15].…”

Section: Discussionmentioning

confidence: 99%

Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing

Park

Shim

2020

Cancer Res Treat

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PurposeEpidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) are ‘must-test’ biomarkers in the molecular diagnostics of advanced-stage lung cancer patients. Although single-gene assays are currently considered the gold standard for these genes, next-generation sequencing (NGS) tests are being introduced to clinical practices. We compared the results of current diagnostics and aimed to suggest timely effective guidance for their clinical use. Materials and MethodsPatients with lung cancer who received both conventional single-gene assays and subsequent targeted NGS testing were enrolled, and the results of their tests were compared. ResultsA total of 241 patients were enrolled, and the EGFR real-time polymerase chain reaction, ALK fluorescence in situ hybridization (FISH), and ROS1 FISH assays exhibited 92.9%, 99.6%, and 99.5% concordance with the NGS tests, respectively. The discordant cases were mostly false-negatives of the single-gene assays, probably due to technical limitation. Of 158 cases previously designated as wild-type, EGFR, ALK, and ROS1 alterations were identified in 10.1%, 1.9%, and 1.3%, respectively, and other targetable alterations were identified in 36.1% of the cases. Of patients with additionally identified actionable alterations, 32.6% (31/95) received matched therapy with a clinical benefit of 48.4% (15/31). ConclusionEven though the conventional and NGS methods were concordant in the majority of cases, NGS testing still revealed a considerable number of additional EGFR, ALK, and ROS1 alterations, as well as other targetable alterations, in Korean advanced-stage lung cancer patients. Given the high frequency of EGFR and other targetable mutations identified in the present study, NGS testing is highly recommended in the diagnosis of Korean lung cancer patients.

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“…In another report, a patient with co-existence of I706T and G719A had a good response and a PFS of at least 22 months, but a patient with co-existence of E709K and G719A had a very poor response to EGFR TKI [ 27 ]. Kauffmann-Guerrero et al reported a patient with co-existence of G857E and R836R in exon 21, who had a very poor response to EGFR TKI [ 12 ]. In our current study, interestingly, all of five patients with stage IV adenocarcinoma harboring a sensitizing mutation and a resistant uncommon mutation involved two point mutations in a single exon (exon 18 G719X with another exon 18 point mutation).…”

Section: Discussionmentioning

confidence: 99%

“…Of all EGFR mutations in lung cancer, approximately 90% are common mutations, including in-frame deletions in exon 19 and an L858R point mutation in exon 21 [ 5 , 6 , 7 ]. However, many uncommon mutations, also called rare or non-classical mutations, were detected but the response to EGFR TKIs was inconsistent due to a limited number of cases enrolled in the trials [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. For example, Chiu et al claimed that both gefitinib and erlotinib are active in lung adenocarcinoma patients with G719X/L861Q/S768I mutations but they had short PFS (a median of 7.7 months) than in those with common EGFR mutations (a median of 11.4 months) ( p < 0.01) [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

Tsai

Hung

Lee

et al. 2018

Cancers

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Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.

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NSCLC Patients Harbouring Rare or Complex EGFR Mutations Are More Often Smokers and Might Not Benefit from First-Line Tyrosine Kinase Inhibitor Therapy

Cited by 16 publications

References 21 publications

<p>Impact of smoking on frequency and spectrum of <em>K-RAS</em> and <em>EGFR </em>mutations in treatment naive Indonesian lung cancer patients</p>

<p>Impact of smoking on frequency and spectrum of <em>K-RAS</em> and <em>EGFR </em>mutations in treatment naive Indonesian lung cancer patients</p>

Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing

Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

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