In the third-line setting , for patients who have not received erlotinib or gefitinib , treatment with erlotinib is recommended .
There are insufficient data to recommend routine third-line cytotoxic therapy .
Purpose To provide evidence -based recommendations to up date the American Society of Clinical Oncology guideline on systemic therapy for stage IV non – small-cell lung cancer ( NSCLC ) .
Results This guideline up date reflects changes in evidence since the previous guideline .
AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer.
BACKGROUND The EGFR T790 M mutation is the most common mechanism of drug resistance to epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors in patients who have lung cancer with an EGFR mutation ( EGFR-mutated lung cancer ) . In pre clinical models , the EGFR inhibitor AZD9291 has been shown to be effective against both EGFR tyrosine kinase inhibitor-sensitizing and T790 M resistance mutations . METHODS We administered AZD9291 at doses of 20 to 240 mg once daily in patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with EGFR tyrosine kinase inhibitors . The study included dose-escalation cohorts and dose-expansion cohorts . In the expansion cohorts , pre study tumor biopsies were required for central determination of EGFR T790 M status . Patients were assessed for safety , pharmacokinetics , and efficacy . RESULTS A total of 253 patients were treated . Among 31 patients enrolled in the dose-escalation cohorts , no dose-limiting toxic effects occurred at the doses evaluated . An additional 222 patients were treated in five expansion cohorts . The most common all-cause adverse events were diarrhea , rash , nausea , and decreased appetite . The overall objective tumor response rate was 51 % ( 95 % confidence interval [ CI ] , 45 to 58 ) . Among 127 patients with central ly confirmed EGFR T790 M who could be evaluated for response , the response rate was 61 % ( 95 % CI , 52 to 70 ) . In contrast , among 61 patients without central ly detectable EGFR T790 M who could be evaluated for response , the response rate was 21 % ( 95 % CI , 12 to 34 ) . The median progression-free survival was 9.6 months ( 95 % CI , 8.3 to not reached ) in EGFR T790M-positive patients and 2.8 months ( 95 % CI , 2.1 to 4.3 ) in EGFR T790M-negative patients . CONCLUSIONS AZD9291 was highly active in patients with lung cancer with the EGFR T790 M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors . ( Funded by AstraZeneca ; Clinical Trials.gov number , NCT01802632 . )
In the third-line setting , for patients who have not received erlotinib or gefitinib , treatment with erlotinib is recommended .
There are insufficient data to recommend routine third-line cytotoxic therapy .
Purpose To provide evidence -based recommendations to up date the American Society of Clinical Oncology guideline on systemic therapy for stage IV non – small-cell lung cancer ( NSCLC ) .
Results This guideline up date reflects changes in evidence since the previous guideline .