Dramatic intracranial response to osimertinib in a poor performance status patient with lung adenocarcinoma harboring the epidermal growth factor receptor T790M mutation: A case report

Uemura, Takashi; Oguri, Tetsuya; Okayama, Minami; Furuta, Hiromi; Kanemitsu, Yoshihiro; Takakuwa, Osamu; Ohkubo, Hirotsugu; Takemura, Masashi; Maeno, Ken; Ito, Yutaka

doi:10.3892/mco.2017.1181

Cited by 10 publications

(8 citation statements)

References 18 publications

(16 reference statements)

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“…The NCCN Guidelines for NSCLC recommend osimertinib (regardless of T790M status) or weekly pulse erlotinib for patients with EGFR‐mutated NSCLC and progressive LM . Osimertinib has shown promising activity in patients with LM, with a number of case studies reporting the efficacy of osimertinib 80 mg once daily for treating patients with refractory LM following prior treatment with EGFR‐TKIs, chemotherapy, SRS, and WBRT . The efficacy of osimertinib 160 mg once daily for patients with heavily pretreated LM is also being assessed in the phase I BLOOM study.…”

Section: Egfr‐tkismentioning

confidence: 99%

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Central Nervous System Metastases from Non-Small Cell Lung Cancer

Ahluwalia¹,

Becker

Levy

2018

The Oncologist

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Historically, treatment options for patients who develop central nervous system (CNS) metastases have been limited and associated with poor outcomes. The development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has improved outcomes for patients with EGFR-mutated disease, and emerging data have demonstrated the ability of these drugs to cross the blood-brain barrier and elicit significant intracranial responses. Recent studies have indicated a role for next-generation EGFR-TKIs, such as osimertinib, in the treatment of CNS metastases. In the context of an evolving treatment paradigm, treatment should be individualized to the patient and requires a multidisciplinary approach.

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Section: Egfr‐tkismentioning

confidence: 99%

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Central Nervous System Metastases from Non-Small Cell Lung Cancer

Ahluwalia¹,

Becker

Levy

2018

The Oncologist

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“…T790M mutation was detected in samples taken from a metastatic pleural tumor or primary lung tumor but results from liquid biopsy was unavailable in the two previous case reports ( 10 , 11 ). We detected T790M mutation in metastatic bone tumor but the result of liquid biopsy was negative.…”

Section: Discussionmentioning

confidence: 93%

“…The clinical efficacy of osimertinib in patients with EGFR harboring T790M mutation and with poor performance status has been previously reported in only two cases ( 10 , 11 ). Both previous cases had also advanced lung adenocarcinoma with brain metastasis, received therapy with combined chemotherapy or with first-line TKI (gefitinib, erlotinib or afatinib), were diagnosed as having tumor positive for T790M mutation during disease progression, and showed dramatic response to osimertinib therapy despite poor performance status ( 10 , 11 ). Osimertinib-related adverse effect (leukopenia) was reported only in one of the two previously reported cases ( 11 ).…”

Section: Discussionmentioning

confidence: 97%

“…Both previous cases had also advanced lung adenocarcinoma with brain metastasis, received therapy with combined chemotherapy or with first-line TKI (gefitinib, erlotinib or afatinib), were diagnosed as having tumor positive for T790M mutation during disease progression, and showed dramatic response to osimertinib therapy despite poor performance status ( 10 , 11 ). Osimertinib-related adverse effect (leukopenia) was reported only in one of the two previously reported cases ( 11 ). Our current patient showed no adverse effect during osimertinib administration.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy of osimertinib in a patient with non‑small cell lung cancer harboring epithelial growth factor receptor exon 19 deletion/T790M mutation, with poor performance status

et al. 2017

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Osimertinib, a third-generation epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor, has been demonstrated to be effective for treating patients with T790M-positive advanced non-small cell lung cancer (NSCLC) with a relatively good performance status (grade 0–1). Reports of therapeutic response to osimertinib in advanced NSCLC patients with poor performance status are infrequent. The present case report discusses a patient with advanced lung adenocarcinoma harboring EGFR exon 19 deletion and T790M mutation with central nervous system involvement and poor performance status. The patient had a past history of partial lung resection due to lung adenocarcinoma, positive genetic test for EGFR exon 19 deletion in post-surgical tumor specimens, and therapy with erlotinib and onartuzumab for the appearance of a lung metastatic tumor during the post-surgical follow-up. The combined therapy was continued until the discovery of metastatic tumors in bones and the central nervous system. The Cobas test performed using tissue from bone metastatic tumor was positive for exon 19 deletion and for T790M mutation. The patient was treated with osimertinib and adverse effects or hematological toxicity were not observed. Performance status of the patient improved from grade 4 to 2. Subsequent studies revealed remission of bone metastasis and reduced central nervous system lesions. This report provides evidence on the safety and efficacy of osimertinib for treating NSCLC patients with progressive disease, central nervous system lesion and poor performance status.

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“…Osimertinib, a third-generation EGFR-TKI, was recently approved for use in NSCLC patients who have been previously treated with EGFR-TKIs and/or chemotherapy and who harbor the EGFR T790M mutation (5,6). Early results from a phase I study (BLOOM) indicate that osimertinib is effective for LM treatment, regardless of whether there is a T790M mutation (7).…”

Section: Introductionmentioning

confidence: 99%

Treatment response to osimertinib in a patient with leptomeningeal metastasis from lung adenocarcinoma following failure of gefitinib and erlotinib: A case report

Liu

Yuan

2018

mol clin onc

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Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective in the treatment of advanced non-small-cell lung cancer (NSCLC) with leptomeningeal metastases (LM); however, a proportion of the patients with resistant tumors do not benefit from EGFR-TKI treatment. In the present study the case of a female patient with advanced lung adenocarcinoma harboring the EGFR L858R mutation (encoded in exon 21) who developed intracranial metastases following treatment with erlotinib after gefitinib failure is reported. The patient achieved a partial response (PR) after four cycles of chemotherapy with pemetrexed/cisplatin. However, after 4 months, LM were detected. The patient was treated with osimertinib, a third-generation EGFR-TKI, but the LM continued to progress and the patient eventually succumbed to the disease (overall survival, 6 months). Therefore, LM in patients without the EGFR T790M mutation (encoded in exon 20) appear to be resistant to treatment with the third-generation TKI osimertinib, which may be associated with human epidermal growth factor receptor 2 amplification. Further clinical trials are required to confirm our results.

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Dramatic intracranial response to osimertinib in a poor performance status patient with lung adenocarcinoma harboring the epidermal growth factor receptor T790M mutation: A case report

Cited by 10 publications

References 18 publications

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Central Nervous System Metastases from Non-Small Cell Lung Cancer

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Central Nervous System Metastases from Non-Small Cell Lung Cancer

Efficacy of osimertinib in a patient with non‑small cell lung cancer harboring epithelial growth factor receptor exon 19 deletion/T790M mutation, with poor performance status

Treatment response to osimertinib in a patient with leptomeningeal metastasis from lung adenocarcinoma following failure of gefitinib and erlotinib: A case report

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