AstraZeneca Canada announces that Health Canada has granted full approval (Notice of Compliance) for Tagrisso (osimertinib) for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC) whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.

...- Patients with histologically confirmed, by the National Cancer Institute (NCI) Laboratory of Pathology or by Clinical Laboratory Improvement Amendments of 1988 (CLIA)-certified Next Generation Sequencing or Cobas estimated Epidermal Growth Factor Receptor (EGFR) Mutation Test v1/2 at an outside institution, advanced lung adenocarcinoma with EGFR-sensitizing somatic mutations or a germline T790M mutation (detected histologically or via circulating tumor deoxyribonucleic acid (ctDNA) analysis using a CLIA assay) with:...

CONTRADICTING EVIDENCE:...an 85-year-old male clinically diagnosed with primary lung cancer at the age of 78 years. His post-operative pathologic staging was adenocarcinoma pT1aN0M0, Stage A1, and he was positive for the epidermal growth factor receptor(EGFR)….The results showed a T790M gene mutation, and osimertinib was administered to treat the metastases. The brain metastasis decreased, and PS improved. Thus, he was discharged from the hospital.

CONTRADICTING EVIDENCE...treated two elderly patients with de novo EGFR T790M mutations with osimertinib as the first-line therapy. We found that the first-line treatment with osimertinib was safe and resulted in a long-term response in elderly patients with de novo EGFR T790M-mutated lung adenocarcinoma.

A man with recurrent lung adenocarcinoma harboring an EGFR exon 19 deletion received erlotinib for 10 months following curative surgery and adjuvant chemotherapy. However, he switched to osimertinib after repeat biopsy showed EGFR exon 19 deletion and T790M mutation leading to erlotinib resistance. His disease progressed after 15 months and repeat biopsy showed SCLC. Next-generation sequencing of peripheral blood detected EGFR exon 19 deletion, T790M mutation, cis-C797S mutation, and RB1 inactivation.

She was also suffered from lung adenocarcinoma in her right upper lobe and bone metastasis in her right scapula at her age of 37. She was treated with gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) because of EGFR mutation (L747-S752 del)...The secondary treatment with osimertinib, an another EGFR-TKI, can successfully control the tumors for over 2 years. This TP53 mutation (R33Vfs*12) was first found in lung adenocarcinomas. The therapeutic effect of osimertinib for this triple mutant lung adenocarcinoma is better than the previous report.

CONTRADICTING EVIDENCE: We identified germline EGFR T790M mutation in the patient's lung adenosquamous carcinoma. He was treated with osimertinib, and achieved complete response (CR) for more than 30 months, without significant drug-related adverse events. Genetic testing showed that germline EGFR T790M mutation might be a characteristic of inherited lung cancer.

A 62-year-old woman with no history of smoking came into the clinic with pleural effusion (PE) in May 2013; stage IV lung adenocarcinoma…subsequent first-generation EGFR TKI treatments for EGFR exon 19 deletion…Geneseeq panel (Geneseeq Technology, Toronto, Ontario, Canada) covering 425 cancer-relevant genes revealed EGFR T790M mutation. Consequently, the patient received osimertinib (80 mg daily) (Fig. 1A) and achieved stable disease in a month...After 8 months of progression-free survival (PFS), the patient experienced development of a new lesion...Genetic testing of circulating tumor DNA from the PE revealed a newly acquired C797S mutation in cis with T790M.

We describe herein a patient whose tumor acquired an EGFR C797S mutation after treatment with a third-generation EGFR TKI. The acquired EGFR C797S should confer resistance to all third-generation EGFR TKIs, similar to the emergence of EGFR T790M and its cross-resistance to all first-generation EGFR TKIs.

Here, we present an in vivo imaging model for brain tumors using human cancer cell lines, including the EGFR-L858R/T790M-positive H1975 lung adenocarcinoma cells...KM12SM colorectal cancer cells containing the TPM3-NTRK1 gene fusion. Human lung adenocarcinoma H1975 cells, harboring an EGFR‐L858R‐sensitive mutation or an EGFR‐T790M‐resistant mutation, were resistant to the first‐generation EGFR‐TKI gefitinib, but were sensitive to the third‐generation EGFR‐TKI osimertinib.