Primary resistance to osimertinib due to SCLC transformation: Issue of T790M determination on liquid re-biopsy

Minari, Roberta; Bordi, Paola; Re, Marzia Del; Facchinetti, Francesco; Mazzoni, Francesca; Barbieri, Fausto; Camerini, Andrea; Comin, Camilla E.; Gnetti, Letizia; Azzoni, Cinzia; Nizzoli, Rita; Bortesi, Beatrice; Rofi, Eleonora; Petreni, Paolo; Campanini, Nicoletta; Rossi, Giulio; Danesi, Romano; Tiseo, Marcello

doi:10.1016/j.lungcan.2017.11.011

Cited by 85 publications

(79 citation statements)

References 23 publications

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“…A recent case series reported by Minari et al presented five patients treated with osimertinib after T790M detection on liquid biopsy, but presented a disease progression at first tumour assessment mediated by SCLC transformation, as evidenced at tissue re‐biopsies. All the patients showed low T790M/activating mutation ratio in the blood before osimertinib treatment (lower than 0.03) . Minari et al suggested that for patients with a low T790M/activating mutation ratio, tissue biopsy should be considered to exclude the presence of SCLC transformation or other concomitant resistance mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Primary resistance to osimertinib despite acquired T790M

Chang

Shih

2020

Respirology Case Reports

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Current National Comprehensive Cancer Network (NCCN) guidelines suggest plasma-based testing (liquid biopsy) for T790M in epidermal growth factor receptor (EGFR)-mutated non-small cell lung carcinoma (NSCLC) with acquired resistance to first-/second-generation EGFR tyrosine kinase inhibitors (TKIs). Positivity for resistant mutation on liquid biopsy may obviate the need for invasive tissue biopsy. We report a rare case of primary resistance to osimertinib, although liquid biopsy revealed EGFR T790M positivity. A 63-year-old male, never smoker, was diagnosed with stage IV lung adenocarcinoma with EGFR exon 19 deletion. Treatment started with erlotinib and was continued for 15 months until disease progression. Osimertinib was initiated when liquid biopsy showed EGFR T790M positivity. However, primary resistance to osimertinib was noted on follow-up imaging. Re-biopsy revealed small cell lung cancer. Detection of T790M via liquid biopsy among NSCLC patients with acquired resistance to EGFR-TKI might miss other possible resistant mechanisms. Tissue biopsy should be considered to exclude small cell lung carcinoma (SCLC) transformation.

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Section: Discussionmentioning

confidence: 99%

Primary resistance to osimertinib despite acquired T790M

Chang

Shih

2020

Respirology Case Reports

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“…[27][28][29] However, these noninvasive liquid biopsies cannot identify the full spectrum of mutations possibly affecting clinical outcomes due to the limited number of genes analyzed (typically 68 to 70 genes) or other concomitant resistant mechanisms. 9,27,30 Furthermore, cell-free DNA analysis might miss actionable mutations, which could be a result of small tumor volume or intratumor heterogeneity resulting in very low frequencies. 27,28,31 Therefore, comprehensive analysis of genomic alterations in tumor tissues via high-throughput panel sequencing can be advantageous to understand the genetic mechanisms associated with tumor progression and therapeutic resistance.…”

Section: Discussionmentioning

confidence: 99%

Concurrent Genetic Alterations Predict the Progression to Target Therapy in EGFR-Mutated Advanced NSCLC

Kim

Lee

Shim

et al. 2019

Journal of Thoracic Oncology

106

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“…SCLC transformation due to osimertinib is rare, and its frequency is still unknown. To our knowledge, only nine cases of SCLC transformation after osimertinib treatment have been reported [6][7][8][9][10] (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Transformation of epidermal growth factor receptor T790M mutation‐positive adenosquamous carcinoma of the lung to small cell carcinoma and large‐cell neuroendocrine carcinoma following osimertinib therapy: an autopsy case report

Moriguchi

Uruga

Fujii

et al. 2019

Respirology Case Reports

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A 59‐year‐old man with relapsed epidermal growth factor receptor ( EGFR ) exon 19 deletion‐positive stage IA adenosquamous carcinoma after lobectomy was treated with erlotinib and bevacizumab for 1 year followed by erlotinib alone for 1 year. Because of mediastinal and supraclavicular lymphadenopathy and a nodule on the left anterior chest wall, the patient underwent repeat biopsy from the supraclavicular lymph node. Pathological analysis demonstrated adenosquamous carcinoma harbouring EGFR exon 19 deletion and T790M mutation. Osimertinib treatment was therefore started. Six months later, the patient underwent a second‐repeat biopsy from the mediastinal lymph nodes and liver metastases. Both specimens showed small cell lung carcinoma (SCLC). After chemotherapies for SCLC, he died from lung cancer. An autopsy demonstrated tumour heterogeneity, including histological types of adenosquamous, SCLC, and large‐cell neuroendocrine carcinoma. Repeat biopsies at the time of disease progression are useful to choose subsequent treatment for patients with EGFR mutation‐positive lung cancer.

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Primary resistance to osimertinib due to SCLC transformation: Issue of T790M determination on liquid re-biopsy

Cited by 85 publications

References 23 publications

Primary resistance to osimertinib despite acquired T790M

Primary resistance to osimertinib despite acquired T790M

Concurrent Genetic Alterations Predict the Progression to Target Therapy in EGFR-Mutated Advanced NSCLC

Transformation of epidermal growth factor receptor T790M mutation‐positive adenosquamous carcinoma of the lung to small cell carcinoma and large‐cell neuroendocrine carcinoma following osimertinib therapy: an autopsy case report

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