Frequency of EGFR T790M mutation and multimutational profiles of rebiopsy samples from non-small cell lung cancer developing acquired resistance to EGFR tyrosine kinase inhibitors in Japanese patients

Ko, Ryo; Kenmotsu, Hirotsugu; Serizawa, Masakuni; Koh, Yasuhiro; Wakuda, Kazushige; Ono, Akira; Taira, Tetsuhiko; Naito, Tateaki; Murakami, Haruyasu; Isaka, Mitsuhiro; Endo, Masahiro; Nakajima, Takashi; Ohde, Yasuhisa; Yamamoto, Nobuyuki; Takahashi, Kazuhisa; Takahashi, Toshiaki

doi:10.1186/s12885-016-2902-0

Cited by 45 publications

(49 citation statements)

References 29 publications

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“…Thirdly, T790M prevalence may be low in real world clinical practice, as a result of several confounding factors, including poor sample quality and DNA denaturation. Our results were similar to those of several retrospective studies conducted in Japan, which reported that the prevalence of T790M mutations is 33–34% in real world clinical practice …”

Section: Discussionsupporting

confidence: 91%

“…Various resistance mechanisms have been identified. Understanding such mechanisms is critical to guide further treatment for patients with EGFR‐TKI resistant NSCLC . Among the EGFR‐TKI resistance mechanisms, T790M mutations, which substitute threonine (T) with methionine (M) at position 790 of exon 20 of the EGFR gene are the most common, accounting for more than 50% .…”

Section: Introductionmentioning

confidence: 99%

“…Among the EGFR‐TKI resistance mechanisms, T790M mutations, which substitute threonine (T) with methionine (M) at position 790 of exon 20 of the EGFR gene are the most common, accounting for more than 50% . Other resistance mechanisms include amplification of the MET gene, PIK3CA and BRAF mutations, epithelial‐to‐mesenchymal transition, and small cell lung cancer transformation . Thus, re‐biopsy of sufficient tissue for molecular analysis is necessary to identify the resistance type and guide further treatment decisions after EGFR‐TKI treatment failure …”

Section: Introductionmentioning

confidence: 99%

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Feasibility of re‐biopsy and EGFR mutation analysis in patients with non‐small cell lung cancer

Kim

Kho

et al. 2018

Thoracic Cancer

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BackgroundIn cases of EGFR‐tyrosine kinase inhibitor (TKI) failure, re‐biopsy may be useful to understand resistance mechanisms and guide further treatment decisions. However, performing re‐biopsy is challenging because of several hurdles. We assessed the feasibility of re‐biopsy in advanced non‐small cell lung cancer (NSCLC) patients in real‐world clinical practice.MethodsWe retrospectively reviewed the clinical and pathologic data of advanced NSCLC patients who experienced disease progression after previous treatment with EGFR‐TKIs at a single tertiary hospital in Korea between January 2014 and December 2016. Re‐biopsy specimens included small biopsy, surgical tissue, or liquid‐based cytology. EGFR mutation was tested using peptide nucleic acid‐mediated clamping PCR.ResultsOf the 230 NSCLC patients that experienced progression after EGFR‐TKI therapy, 105 (45.7%) underwent re‐biopsy. Re‐biopsy was successfully performed in 94 (89.5%) patients, and 11 patients were diagnosed with no malignancy. The complication rate was 8.6%, including seven cases of pneumothorax. EGFR mutation testing was performed on 75 patients using re‐biopsy specimens. Of the 57 patients who had sensitizing mutations at diagnosis, T790M mutations were found in 19 (33.3%), while 38 (66.7%) had no T790M mutation. Multivariate analysis showed that the re‐biopsy group was younger (P = 0.002) and exhibited a previous response to EGFR‐TKIs (P < 0.001).ConclusionRe‐biopsy in advanced NSCLC is feasible in real world clinical practice, particularly in younger patients and those who achieved a previous response to EGFR‐TKIs.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Feasibility of re‐biopsy and EGFR mutation analysis in patients with non‐small cell lung cancer

Kim

Kho

et al. 2018

Thoracic Cancer

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“…However, mutations in the T790M gene account only for 50% of all resistance mutations. Mutations also involves other genes and gene amplification[31,32]. Therefore, we may need more monitorings in order to detect resistance timely.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of plasma EGFR ctDNA in NSCLC patients treated with EGFR-TKIs

Zhang

Wei

et al. 2017

PLoS ONE

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ObjectiveEpidermal growth factor receptor (EGFR) specific mutations have been known to improve survival of patients with non-small-cell lung carcinoma (NSCLC). However, whether there are any changes of EGFR mutations after targeted therapy and its clinical significance is unclear. This study was to identify the status of EGFR mutations after targeted therapy and predict the prognostic significance for NSCLC patients.MethodsA total of forty-five (45) NSCLC patients who received EGFR-TKI therapy were enrolled. We identified the changes of EGFR mutations in plasma ctDNA by Amplification Refractory Mutation System (ARMS) PCR technology.ResultsIn the 45 cases of NSCLC with EGFR mutations, the EGFR mutation status changed in 26 cases, in which, 12 cases (26.7%) from positive to negative, and 14 cases (31.1%) from T790M mutation negative to positive after TKI targeted therapy. The T790M occurance group had a shorter Progression -Free-Survival (PFS) than the groups of EGFR mutation undetected and EGFR mutation turned out to have no change after EGFR-TKI therapy (p < 0.05).ConclusionsAccording to this study, it’s necessary to closely monitor EGFR mutations during follow-up to predict the prognosis of NSCLC patients who are to receive the TKI targeted therapy.

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“…Acquired resistance to EGFR‐TKIs is mainly attributed to secondary EGFR mutations . EGFR T790M, a specific point mutation in exon 20, is the most common resistance mutation, and accounts for 33–63% . Third‐generation EGFR‐TKIs (3‐TKIs), such as osimertinib, have proven to have promising activity in advanced NSCLC patients with EGFR T790M mutations .…”

Section: Introductionmentioning

confidence: 99%

Re‐biopsy and liquid biopsy for patients with non‐small cell lung cancer after EGFR‐tyrosine kinase inhibitor failure

Zhou

Zhao

et al. 2019

Thoracic Cancer

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Background Re‐biopsy is important for exploring resistance mechanisms, especially for non‐small cell lung cancer (NSCLC) patients who develop resistance to EGFR‐tyrosine kinase inhibitors (TKIs). Liquid biopsy using circulating tumor DNA has come into use for this purpose. This retrospective study investigated the status of re‐biopsy and liquid biopsy in NSCLC patients with EGFR mutations and evaluated their effect on clinical strategies and prognosis. Methods Five hundred fifty‐five NSCLC patients with resistance to EGFR‐TKIs were included and divided into three groups: re‐biopsy, liquid biopsy, and no re‐biopsy. Amplification refractory mutation system (ARMS) PCR or super ARMS PCR was used to detect EGFR mutations. Results Three hundred eight (55.5%) patients underwent re‐biopsy; 45.5% (140/308) were positive for T790M. The most common re‐biopsy procedure was computed tomography‐guided percutaneous core needle biopsy (60.1%), followed by effusion drainage (29.5%) and superficial lymph node biopsy (6.5%). One hundred eighteen (21.3%) patients underwent liquid biopsy; the T790M detection rate was 41.5% (49/118.) Of the 308 patients who underwent re‐biopsy, 69 were examined for EGFR mutations with plasma. The concordance rate of T790M detection between tissue and plasma was 66.7%. A statistical difference in further treatment after EGFR‐TKI failure was observed among all groups ( P = 0.014). Patients in the biopsy groups were more likely to receive third‐generation EGFR‐TKIs. Multivariate analysis showed that re‐biopsy had a significant impact on overall survival ( P < 0.001). Conclusion Re‐biopsy plays a pivotal role in the management of patients with NSCLC and resistance to EGFR‐TKIs. Liquid biopsy may be an alternative if difficulties performing re‐biopsy exist.

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Frequency of EGFR T790M mutation and multimutational profiles of rebiopsy samples from non-small cell lung cancer developing acquired resistance to EGFR tyrosine kinase inhibitors in Japanese patients

Cited by 45 publications

References 29 publications

Feasibility of re‐biopsy and EGFR mutation analysis in patients with non‐small cell lung cancer

Feasibility of re‐biopsy and EGFR mutation analysis in patients with non‐small cell lung cancer

Prognostic value of plasma EGFR ctDNA in NSCLC patients treated with EGFR-TKIs

Re‐biopsy and liquid biopsy for patients with non‐small cell lung cancer after EGFR‐tyrosine kinase inhibitor failure

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