...to be included in the study patients should present at least one EGFR mutation (exon 19 deletion or L858R with or without T790M)....

Patients with advanced EGFR-mutant NSCLC were given concurrent gefitinib (250 mg orally daily) and 3-week cycle of carboplatin plus pemetrexed for 4 to 6 cycles, followed by gefitinib maintenance until disease progression or unacceptable toxicity….There were 17 subjects with progressive diseases tested for EGFR T790M mutations, and 11 cases were positive for T790M mutations.

CONTRADICTING EVIDENCE: Uncommon mutation categories were: major uncommon (G719X, L861Q, S768I; 73%); compound (35%); ex20ins (12%); T790M (7%); other (9%). Most pts (n = 226; 92%) were treated in 1st-line with an EGFR TKI; 132 (54%), 70 (28%), 35 (14%) and 7 (3%) received afatinib, gefitinib, erlotinib and osimertinib....Overall median OS was 24.4 mos....ORR was 42% overall (major: 50%; compound: 49%; other: 44%; T790M: 20%; ex20ins: 17%); afatinib: 44% (DoR: 12.0 mos); 1st-gen TKIs: 44% (DoR: 11.0 mos)....Response was highest in pts with major uncommon, and/or compound mutations.

A total of 176 patients with EGFR-mutant stage IIIB-IV relapsed or metastatic NSCLC and received first-generation EGFR-TKI gefitinib or erlotinib monotherapy (T; n=88) or combined with bevacizumab (A+T; n=88)...At progression, EGFR T790M, detected from 35% in the A+T group and 42% in the T group, was the major resistance mechanism in both groups.

... epidermal growth factor receptor (EGFR) kinase domain mutations are a common cause of non-small-cell lung cancer (NSCLC), a major subtype of lung cancers. Patients harboring most of these mutations respond well to the EGFR inhibitors Gefitinib and Erlotinib initially, but soon develop resistance to them due to the emergence of the gatekeeper mutation T790M.

Non-small cell lung cancers carrying activating mutations in the gene for the epidermal growth factor receptor (EGFR) are highly sensitive to EGFR-specific tyrosine kinase inhibitors....A secondary T790M mutation of EGFR accounted for half the tumors with acquired resistance to gefitinib in Japanese patients.

Two patients with classic activating mutations exhibited de novo gefitinib resistance and had concurrent genetic anomalies usually associated with acquired TKI resistance, specifically the T790M EGFR mutation and MET amplification.

An 85-year-old man with advanced NSCLC with brain andbone metastasis was initially treated with gefitinib targeted therapy. After 4 months treatment, the patient developed drug resistance and a second genetic testing revealed that the T790M mutation was positive.

Here we report the case of a patient with EGFR-mutant, gefitinib-responsive, advanced non-small-cell lung cancer who had a relapse after two years of complete remission during treatment with gefitinib. The DNA sequence of the EGFR gene in his tumor biopsy specimen at relapse revealed the presence of a second point mutation, resulting in threonine-to-methionine amino acid change at position 790 of EGFR. Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance.

CONTRADICTING EVIDENCE: Quercetin synergistically enhances the therapeutic effect of gefitinib on EGFRT790M-harboring NSCLCs and delays the acquisition of the EGFRT790M mutation.