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

Abstract

Abstract.We herein report a case of dramatic intracranial response to osimertinib in a poor performance status patient with lung adenocarcinoma harboring the epidermal growth factor receptor (EGFR) T790M mutation encoded in exon 20. The patient was a 59-year-old woman with EGFR exon 19 deletion-positive lung adenocarcinoma, who relapsed with multiple brain metastases. Computed tomography-guided biopsy of the left pleural tumor revealed adenocarcinoma harboring an EGFR exon 19 deletion and an EGFR T790M mutation encoded in exon 20. The patient was treated with osimertinib, a third-generation EGFR tyrosine kinase inhibitor. Two days after treatment initiation, the patient displayed profound disturbance of consciousness, possibly due to carcinomatous meningitis, and treatment had to be discontinued due to difficulty in taking osimertinib. However, the patient gradually started to recover consciousness and, after 3 days, she was again able to take osimertinib. One month after the initiation of osimertinib treatment, magnetic resonance imaging revealed an apparent reduction in brain metastases. The patient is currently under continued treatment with osimertinib. At the last follow-up (February, 2017) she exhibited partial response to the treatment.

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

“…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.…”

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

“…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.…”

“…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 ).…”

“…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.…”

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

“…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).…”