Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated non-small cell lung cancer except both exon 19 deletion and exon 21 L858R: A retrospective analysis in Korea

Baek, Jin Ho; Sun, Jong Mu; Min, Young Joo; Cho, Eun Kyung; Cho, Byoung Chul; Kim, Joo Hang; Ahn, Myung Ju; Park, Keunchil

doi:10.1016/j.lungcan.2014.11.013

Cited by 77 publications

(53 citation statements)

References 32 publications

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“…The response rate (RR) of patients with rare and complex mutations treated with TKIs was 47% (95% CI; 23%–72%), while the rate of disease control (DCR) was 65% (95 % CI; 38%–86%). Similar findings have already been reported in other studies [41] in which RR to TKIs varies between 34% and 50% and the DCR between 57.4% and 75.6%, in any case lower than those of common mutations for which RR is greater than 60% for both first and second generation drugs.…”

Section: Discussionsupporting

confidence: 91%

“…These findings agree with published results, reporting low, although heterogeneous, response rates (0% to 37%) and dismal prognosis (median PFS from 1.3 to 6.3 months). [19, 28, 41] A post hoc analysis of NEJ002 study showed lower efficacy of gefitinib than chemotherapy in people with G719X and L861Q mutations, without significant differences between the two mutations [18]. In contrast, in subjects with G719X mutation (alone or in combination) treated with afatinib both RR and median PFS (77.8% and 13.8 months, respectively) are greater than those receiving chemotherapy [9], thus suggesting second-generation TKIs as a possible option in this mutations class [21].…”

Section: Discussionmentioning

confidence: 99%

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Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations

et al. 2017

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IntroductionTyrosine-kinase inhibitors (TKIs) represent the best treatment for advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon 21 epidermal growth factor receptor mutation (EGFRm). This is an observational study investigating epidemiology, clinical features and treatment outcome of NSCLC cases harbouring rare/complex EGFRm.ResultsAmong 764 non-squamous NSCLC cases with known EGFRm status, 26(3.4%) harboured rare/complex EGFRm. Patients receiving first-line TKIs (N = 17) achieved median Progression Free Survival (PFS) and Overall Survival (OS) of 53 (IC 95%, 2–105) and 84 (CI 95%, 27–141) weeks respectively, without significant covariate impact. Response Rate and Disease Control Rate (DCR) were 47% and 65%, respectively. Uncommon exon 19 mutations achieved longer OS and PFS and higher DCR compared with exon 18 and 20 mutations. No additional gene mutation was discovered by MassARRAY analysis. TKIs were globally well tolerated.Materials and methodsA retrospective review of advanced non-squamous NSCLC harbouring rare/complex EGFRm referred to our Center between 2010 and 2015 was performed. Additional molecular pathways disregulation was explored in selected cases, through MassARRAY analysis.ConclusionsPeculiar clinical features and lower TKIs sensitivity of uncommon/complex compared with common EGFRm were shown. Exon 19 EGFRm achieved the best TKIs treatment outcome, while the optimal treatment of exon 18 and 20 mutations should be further clarified.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations

et al. 2017

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“…The heterogeneities of the studies mainly consist of demographic features, stage and histological classification of the tumor, different treatment lines and inconsistency in the criteria for response assessment. Additionally, the exclusion of 3 studies of which the original data were inaccessible in our calculation might also cause bias (47,79,80). Although we combined several studies to increase the sample size, it was still far from enough to draw a convincing conclusion on the sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Determining EGFR-TKI sensitivity of G719X and other uncommon EGFR mutations in non-small cell lung cancer: Perplexity and solution

Yang

Liang

et al. 2017

Oncology Reports

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Mutations in epidermal growth factor receptor (EGFR) play critical roles in the pathogenesis of non-small cell lung cancer (NSCLC), and they are highly associated with sensitivity to tyrosine kinase inhibitors (TKIs). While the pathogenic and pharmacological characteristics of common mutations in EGFR have been thoroughly investigated, those of uncommon mutations remain to be elucidated. Traditional approaches to study common mutations by randomized controlled trials are not feasible for uncommon mutations owing to their rarity. Therefore, by systematically reviewing laboratory and clinical studies of the G719X mutation, one of the uncommon mutations, we concluded that the G719X mutation was intermediately sensitive to TKIs, with an average response rate of 35.1% (47/134). Moreover, accordingly, we proposed a comprehensive model to investigate uncommon mutations in EGFR. The model involves both basic and clinical components, composed of structural analyses, functional alterations, cell viabilities and animal models with various types of clinical studies. In this review, we systematically reviewed studies of the G719X mutation and put forward a research model that could be generalized to explore uncommon mutations in diseases associated with gene mutations.

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“…EGFR mutations >10% of allele frequency are listed in Table VII. Although minor mutations were mostly accompanied by major mutations, such as L858R and exon 19 deletion (21,22), gefitinib sensitizing mutations (L833V+H835L) and a resistance mutation (L747S) were also found (23,24). …”

Section: Resultsmentioning

confidence: 99%

Routine genetic testing of lung cancer specimens derived from surgery, bronchoscopy and fluid aspiration by next generation sequencing

Yamamoto

Kikuchi

Kobayashi

et al. 2017

International Journal of Oncology

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After the development of EGFR tyrosine kinase inhibitors (TKIs), genetic testing of EGFR became required for effective treatment of lung cancer. Initially, the testing was conducted separately for each mutated region. However, many EGFR mutations have since been identified that determine the efficacy of EGFR-TKIs. Therefore, genetic testing of EGFR by next generation sequencing (NGS) may be a suitable strategy for lung cancer. Here we examined the applicability of the NGS method in regard to sensitivity, time and cost. A total of 939 specimens were obtained from 686 lung cancer patients at our hospital. DNA and RNA were simultaneously extracted from specimens derived from surgery, bronchoscopy, and fluid aspiration. Specimens included cerebrospinal fluid, pleural effusion, abdominal fluid, and pericardial effusion. From RNA, target regions (EGFR, KRAS, ALK fusion and RET fusion) were enriched by RT-PCR and sequenced with MiSeq. From DNA, PCR or PCR-RFLP conventional methods were performed. NGS and conventional methods were carried out routinely per week. Among the total 939 specimens, 38 specimens could not be examined with NGS. Among these, 34 specimens were analyzed by conventional testing with simultaneously extracted DNA. The remaining four specimens could not be tested with either method. Compared with the conventional method, the concordance rate of mutations was 99% (892/901), excluding specimens with NGS failure. The time period required from processing of specimens to results was 4 days, and the cost per sample was sufficiently low. In conclusion, the genetic testing with NGS method was useful for lung cancer treatment. The cost, sensitivity and time were able to tolerate routine examinations.

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Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated non-small cell lung cancer except both exon 19 deletion and exon 21 L858R: A retrospective analysis in Korea

Cited by 77 publications

References 32 publications

Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations

Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations

Determining EGFR-TKI sensitivity of G719X and other uncommon EGFR mutations in non-small cell lung cancer: Perplexity and solution

Routine genetic testing of lung cancer specimens derived from surgery, bronchoscopy and fluid aspiration by next generation sequencing

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