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  PubMed Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA.
 The present study assesses the efficacy of Osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients.
 Progressing T790M-positive NSCLC patients received Osimertinib (80 mg daily).
  Osimertinib is an irreversible third generation EGFR tyrosine kinase inhibitor (TKI) and has shown outstanding performances in treating EGFR T790M-positive advanced non-small cell lung cancer (NSCLC) patients, but acquired resistance is inevitable.
  In contrast, afatinib treatment reduced proliferation and inhibited EGFR phosphorylation in L858M/L861Q and L858R mutant cells at similar concentrations.
  Brief report: EGFR L858M/L861Q cis mutations confer selective sensitivity to afatinib.
 In contrast, afatinib treatment reduced proliferation and inhibited EGFR phosphorylation in L858M/L861Q and L858R mutant cells at similar concentrations.
  Brief report: EGFR L858M/L861Q cis mutations confer selective sensitivity to afatinib.
 In contrast, afatinib treatment reduced proliferation and inhibited EGFR phosphorylation in L858M/L861Q and L858R mutant cells at similar concentrations.
  Both agents were effective in multiple mouse xenograft models of human lung adenocarcinoma (T790M positive or negative), exhibiting less activity against wild-type EGFR than existing approved EGFR kinase inhibitors (including osimertinib).
  However, patients who treatment by the erlotinib and gefitinib will relapse because of the emergence of drug-resistant mutations,with T790M mutations accounting for approximately 60% of all resistance.
  However, patients who treatment by the erlotinib and gefitinib will relapse because of the emergence of drug-resistant mutations,with T790M mutations accounting for approximately 60% of all resistance.
  Evolutionary modeling suggests that a schedule of twice weekly pulse and daily low-dose erlotinib may delay emergence of EGFR T790M.
 This evolutionary modeling-based dosing schedule was well-tolerated but did not improve progression-free survival or prevent emergence of EGFR T790M, likely due to insufficient peak serum concentrations of erlotinib.
  Specifically, lung ADC patients with stage-IV HER2-mutant tumors treated with chemotherapy or targeted agents, even without afatinib or anti-HER2 targeted therapy, showed similar clinical outcomes to lung ADC patients harboring EGFR exon 19 deletion or L858R mutations (P = 0.870).
  AZD9291, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), benefits patients with T790M mutant non-small-cell lung cancer who fail treatment with first-generation EGFR TKIs.
  Afatinib successfully treated leptomeningeal metastasis during erlotinib treatment in a patient with EGFR-mutant (Exon18:G719S) lung adenocarcinoma as a second-line chemotherapy.
  Afatinib successfully treated leptomeningeal metastasis during erlotinib treatment in a patient with EGFR-mutant (Exon18:G719S) lung adenocarcinoma as a second-line chemotherapy.
  Osimertinib effective in EGFR T790M-positive lung cancer.
  Rapid Acquisition of T790M Mutation after Treatment with Afatinib in an NSCLC Patient Harboring EGFR Exon 20 S768I Mutation.
  Rapid Acquisition of T790M Mutation after Treatment with Afatinib in an NSCLC Patient Harboring EGFR Exon 20 S768I Mutation.
  Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer.
 Methods In this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non-small-cell Lung Cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous Pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance Pemetrexed was allowed.
 Conclusions Osimertinib had significantly greater efficacy than platinum therapy plus Pemetrexed in patients with T790M-positive advanced non-small-cell Lung Cancer (including those with CNS metastases) in whom disease had progressed during first-line EGFR-TKI therapy.
  Methods In this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non-small-cell Lung Cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed.
  Methods In this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non-small-cell Lung Cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed.
  Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer.
 Background Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non-small-cell Lung Cancer.
 Methods In this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non-small-cell Lung Cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral Osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed.
 Conclusions Osimertinib had significantly greater efficacy than platinum therapy plus pemetrexed in patients with T790M-positive advanced non-small-cell Lung Cancer (including those with CNS metastases) in whom disease had progressed during first-line EGFR-TKI therapy.
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