Spatiotemporal T790M Heterogeneity in Individual Patients with EGFR-Mutant Non–Small-Cell Lung Cancer after Acquired Resistance to EGFR-TKI

Hata, Akito; Katakami, Nobuyuki; Yoshioka, Hiroshige; Kaji, Ryuji; Masago, Katsuhiro; Fujita, Shiro; Imai, Yukihiro; Nishiyama, Akihiro; Ishida, Tadashi; Nishimura, Yoshihiro; Yatabe, Yasushi

doi:10.1097/jto.0000000000000647

Cited by 139 publications

(109 citation statements)

References 42 publications

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“…There is a large variety of T790M occurrence (30-83%) after first-generation EGFR TKI treatment [9]. Kuiper et al [10] showed that the incidence of T790M mutation in first post-TKI biopsy in his cohort of EGFR-mutated NSCLC patients was 52%.…”

Section: Discussionmentioning

confidence: 99%

Rapid Intracranial Response to Osimertinib in a Patient with Epidermal Growth Factor Receptor T790M-Positive Adenocarcinoma of the Lung

Reichegger¹,

Jochum²,

Förbs³

et al. 2016

Oncol Res Treat

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Background: Osimertinib (AZD9291, Tagrisso) is a potent, irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Case Report: Our report demonstrates that osimertinib is able to inhibit the growth of a radiotherapy- and surgery-refractory EGFR T790M-positive brain metastasis in a patient with lung adenocarcinoma. Conclusion: These data show that re-biopsy in EGFR-mutated non-small cell lung cancer patients with acquired TKI resistance should be performed.

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Section: Discussionmentioning

confidence: 99%

Rapid Intracranial Response to Osimertinib in a Patient with Epidermal Growth Factor Receptor T790M-Positive Adenocarcinoma of the Lung

Reichegger¹,

Jochum²,

Förbs³

et al. 2016

Oncol Res Treat

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“…The efficacy of osimertinib, a third-generation EGFR-TKI that is effective against the T790M mutant form of EGFR, for such patients is unclear. Furthermore, a recent study found that the CNS metastases including leptomeningeal metastases of 10 of 12 patients whose extracranial tumor was positive for T790M were negative for this mutation (22). If the CNS metastases of most patients with T790M-positive extracranial tumors are indeed T790M negative, then the metastatic lesions may be susceptible to control by first-or second-generation EGFR-TKIs.…”

Section: Egfr-tkis For Treatment Of Brain Metastases (Bm)mentioning

confidence: 99%

Is afatinib a treatment option for brain metastases in patients with EGFR mutation-positive non-small cell lung cancer?

2016

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“…Regardless, the latter clinical distinction might not be relevant because of tumour heterogeneity in the development of acquired resistance to egfr-targeted therapies 29 . Spatial and temporal heterogeneity has been retrospectively described for the T790M resistance mutation 34 .…”

Section: Molecular Testing Of Egfr Mutations In Nsclc: Clinical Perspmentioning

confidence: 99%

Management of Egfr-Mutated Non-Small-Cell Lung Cancer: Practical Implications from a Clinical and Pathology Perspective

Cabanero

Sangha²,

Sheffield

et al. 2017

Current Oncology

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Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have evolved from being histologically described to molecularly defined. Management of lung adenocarcinomas now generally requires multiple molecular tests at baseline to define the optimal treatment strategy. More recently, second biopsies performed at progression in patients treated with tyrosine kinase inhibitors (tkis) have further defined the continued use of molecularly targeted therapy.In the present article, we focus on one molecular subtype: EGFR-mutated nsclc. For that patient population, multiple lines of tki therapy are now available either clinically or in clinical trials. Each line of treatment is guided by the specific mutations (for example, L858R, T790M, C797S) identified in EGFR. We first describe the various mechanisms of acquired resistance to EGFR tki treatment. We then focus on strategies that clinicians and pathologists can both use during tissue acquisition and handling to optimize patient results. We also discuss future directions for the molecular characterization of lung cancers with driver mutations, including liquid biopsies. Finally, we provide an algorithm to guide treating physicians managing patients with EGFR-mutated nsclc. The same framework can also be applied to other molecularly defined nsclc subgroups as resistance patterns are elucidated and additional lines of treatment are developed.

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Spatiotemporal T790M Heterogeneity in Individual Patients with EGFR-Mutant Non–Small-Cell Lung Cancer after Acquired Resistance to EGFR-TKI

Abstract: T790M status in an individual patient can be spatiotemporally heterogeneous because of selective pressure from EGFR-TKI.

Cited by 139 publications

References 42 publications

Rapid Intracranial Response to Osimertinib in a Patient with Epidermal Growth Factor Receptor T790M-Positive Adenocarcinoma of the Lung

Rapid Intracranial Response to Osimertinib in a Patient with Epidermal Growth Factor Receptor T790M-Positive Adenocarcinoma of the Lung

Is afatinib a treatment option for brain metastases in patients with EGFR mutation-positive non-small cell lung cancer?

Management of Egfr-Mutated Non-Small-Cell Lung Cancer: Practical Implications from a Clinical and Pathology Perspective

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