EGFR mutation prevalence in Asia-Pacific and Russian patients with advanced NSCLC of adenocarcinoma and non-adenocarcinoma histology: The IGNITE study

Han, Baohui; Tjulandin, Sergei; Hagiwara, Koichi; Normanno, Nicola; Wulandari, Laksmi; Лактионов, К. К.; Hudoyo, Achmad; He, Yong; Zhang, Yi Ping; Wang, Meng Zhao; Liu, Chien Ying; Ratcliffe, Marianne J.; McCormack, Rose; Reck, Martin

doi:10.1016/j.lungcan.2017.08.021

Cited by 116 publications

(103 citation statements)

References 35 publications

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“…In fact improvement of this routine method maybe possible, which has been shown by incorporating two rounds of PCR amplification of cfDNA yielding high sensitivity up to 60%. Interestingly, the use of ARMS PCR in real‐life testing of paired tumor and plasma samples as shown in IGNITE (n = 2581 patients) and ASSESS (n = 1162) studies has reported 46% sensitivity, which is similar to our findings. However, in clinical trial setting involving 1060 subjects, the use of ARMS PCR can yield up to 65% sensitivity .…”

Section: Discussionsupporting

confidence: 90%

“…The difference with previous study may lie in primer designs and/or PCR equipment being used for HRM screening. In principle, HRM alone will not be able to genotype clinically relevant variants, and careful designs of HRM primers must avoid polymorphic EGFR variants in exons 20 and 21 that do not impact clinical outcome such as Q787Q and R836R …”

Section: Discussionmentioning

confidence: 99%

“…In principle, HRM alone will not be able to genotype clinically relevant variants, 35 and careful designs of HRM primers must avoid polymorphic EGFR variants in exons 20 and 21 that do not impact clinical outcome such as Q787Q and R836R. 30,36 In spite of low sensitivity of our methods to detect EGFR mutations in plasma cfDNA, showed in our study findings, these methods are more feasible, economical, and relatively simple than other more complex methods requiring specialized training to detect EGFR mutations in plasma cfDNA. According to IASLC's recommendation of genotyping cfDNA, the feasibility of platforms to be used to genotyping cfDNA should be a prime concern of each clinical setting in its region.…”

Section: Sensitivity and Specificitymentioning

confidence: 99%

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Evaluation of PCR‐HRM, RFLP, and direct sequencing as simple and cost‐effective methods to detect common EGFR mutations in plasma cell–free DNA of non–small cell lung cancer patients

et al. 2019

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Background Lung cancer patients with mutations in epidermal growth factor receptor (EGFR) gene are treated with tyrosine kinase inhibitor (TKI). Aims We aimed to evaluate polymerase chain reaction (PCR)–high‐resolution melting (HRM), restriction fragment length polymorphism (RFLP), and direct sequencing (DS) to detect EGFR mutations in cell‐free DNA (cfDNA) before and after TKI treatment in real‐world settings of a developing country. Methods Paired cytology and plasma samples were collected from 116 treatment‐naïve lung cancer patients. DNA from both plasma and cytology specimens was isolated and analyzed using PCR‐HRM (to detect exon 19 insertion/deletion), RFLP (to genotypes L858R and L861Q), and DS (to detect uncommon mutations G719A, G719C, or G719S [G719Xaa] in exon 18 and T790M and insertion mutations in exon 20). Results EGFR genotypes were obtained in all 116 (100%) cfDNA and 110/116 (94.82%) of cytological specimens of treatment‐naïve patient (baseline samples). EGFR‐activating mutations were detected in 46/110 (40.6%) plasma samples, and 69/110 (63.2%) mutations were found in routine cytology samples. Using cytological EGFR genotypes as reference, we found that sensitivity and specificity of baseline plasma EGFR testing varied from 9.1% to 39.39% and 83.12% to 96.55%, respectively. In particular, the sensitivity and specificity of this assay in detecting baseline T790M mutations in exon 20 were 30% and 89.58%, respectively. Three months after TKI treatment, plasma T790M and insertion exon 20 mutations appeared in 5.4% and 2.7% patients, respectively. Conclusions Despite low sensitivity, combined DS, RFLP, and PCR‐HRM was able to detect EGFR mutations in plasma cfDNA with high specificity. Moreover, TKI resistance exon 20 insertions mutation was detected as early as 3 months post TKI treatment.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Sensitivity and Specificitymentioning

confidence: 99%

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Evaluation of PCR‐HRM, RFLP, and direct sequencing as simple and cost‐effective methods to detect common EGFR mutations in plasma cell–free DNA of non–small cell lung cancer patients

et al. 2019

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“…The IGNITE study is the largest analysis of real‐world EGFR mutations, with 3382 advanced NSCLC patients from Asia‐Pacific and Russia enrolled . The EGFR mutation rate was 49.3% in adenocarcinoma patients.…”

Section: Discussionmentioning

confidence: 99%

EGFR mutations in early‐stage and advanced‐stage lung adenocarcinoma: Analysis based on large‐scale data from China

Zhang

et al. 2018

Thoracic Cancer

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BackgroundEGFR‐tyrosine kinase inhibitors play an important role in the treatment of advanced non‐small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early‐stage lung adenocarcinoma remain unclear.MethodsWe retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA–IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition.ResultsA total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early‐stage and 949 to the advanced‐stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced‐stage group (P < 0.001). The total EGFR mutation rate in the early‐stage group was similar to that in the advanced‐stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early‐stage and advanced‐stage groups.ConclusionEarly‐stage and advanced‐stage groups exhibited the same EGFR mutation frequencies and types.

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“…Currently, tissue biopsy and cytology samples are considered suitable for molecular testing, provided they are handled appropriately [45]; in addition, the European regulatory agency has recently approved the use of cfDNA when a tumour sample is not available. Results from the recently completed non-interventional Europe-Japan diagnostic study for EGFR testing (ASSESS) [90] and the ongoing interventional diagnostic Asia-Pacific and Russia diagnostic study for EGFR testing (IGNITE) [91] will help to further establish whether cfDNA plasma samples are a suitable and less invasive substitute for tumour tissue [49].…”

Section: Dosage and Administrationmentioning

confidence: 99%

Gefitinib: a review of its use in adults with advanced non-small cell lung cancer

Dhillon

2015

Targ Oncol

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Gefitinib (Iressa®) is a selective small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR TKI) indicated for the treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating mutations of EGFR tyrosine kinase. Large phase III or IV clinical trials in patients with locally advanced or metastatic NSCLC showed that gefitinib as first- or subsequent-line treatment significantly prolonged progression-free survival (PFS) and improved objective response rates and/or health-related quality of life parameters in patients with activating EGFR mutations and in clinically selected patients (e.g., Asian patients or never-smokers) who are more likely to harbour these mutations. Overall survival did not increase significantly with gefitinib, although post-study treatments may have had a confounding effect on this outcome. Gefitinib was generally well tolerated in these studies, with mild or moderate skin reactions, gastrointestinal disturbances and elevations in liver enzymes among the most common adverse reactions in gefitinib recipients; interstitial lung disease has also been reported in <6 % of gefitinib recipients. Compared with chemotherapy, gefitinib as first- or subsequent-line therapy provided similar or greater PFS benefit and was generally associated with fewer haematological adverse events, neurotoxicity, asthenic disorders, as well as grade ≥3 adverse events. Although the position of gefitinib with respect to other EGFR TKIs is not definitively established, current evidence indicates that gefitinib monotherapy is an effective and generally well-tolerated first- or subsequent-line treatment option for patients with NSCLC and activating EGFR mutations who have not received an EGFR TKI previously.

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EGFR mutation prevalence in Asia-Pacific and Russian patients with advanced NSCLC of adenocarcinoma and non-adenocarcinoma histology: The IGNITE study

Cited by 116 publications

References 35 publications

Evaluation of PCR‐HRM, RFLP, and direct sequencing as simple and cost‐effective methods to detect common EGFR mutations in plasma cell–free DNA of non–small cell lung cancer patients

Evaluation of PCR‐HRM, RFLP, and direct sequencing as simple and cost‐effective methods to detect common EGFR mutations in plasma cell–free DNA of non–small cell lung cancer patients

EGFR mutations in early‐stage and advanced‐stage lung adenocarcinoma: Analysis based on large‐scale data from China

Gefitinib: a review of its use in adults with advanced non-small cell lung cancer

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