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 .
Rociletinib in EGFR-mutated non-small-cell lung cancer.
BACKGROUND Non-small-cell lung cancer ( NSCLC ) with a mutation in the gene encoding epidermal growth factor receptor ( EGFR ) is sensitive to approved EGFR inhibitors , but resistance develops , mediated by the T790 M EGFR mutation in most cases . Rociletinib ( CO-1686 ) is an EGFR inhibitor active in pre clinical models of EGFR-mutated NSCLC with or without T790 M . METHODS In this phase 1 - 2 study , we administered rociletinib to patients with EGFR-mutated NSCLC who had disease progression during previous treatment with an existing EGFR inhibitor . In the expansion ( phase 2 ) part of the study , patients with T790M-positive disease received rociletinib at a dose of 500 mg twice daily , 625 mg twice daily , or 750 mg twice daily . Key objectives were assessment of safety , side-effect profile , pharmacokinetics , and preliminary antitumor activity of rociletinib  . Tumor biopsies to identify T790 M were performed during screening . Treatment was administered in continuous 21-day cycles . RESULTS A total of 130 patients were enrolled . The first 57 patients to be enrolled received the free-base form of rociletinib ( 150 mg once daily to 900 mg twice daily ) . The remaining patients received the hydrogen bromide salt ( HBr ) form ( 500 mg twice daily to 1000 mg twice daily ) . A maximum tolerated dose ( the highest dose associated with a rate of dose-limiting toxic effects of less than 33 % ) was not identified . The only common dose-limiting adverse event was hyperglycemia . In an efficacy analysis that included patients who received free-base rociletinib at a dose of 900 mg twice daily or the HBr form at any dose , the objective response rate among the 46 patients with T790M-positive disease who could be evaluated was 59 % ( 95 % confidence interval [ CI ] , 45 to 73 ) , and the rate among the 17 patients with T790M-negative disease who could be evaluated was 29 % ( 95 % CI , 8 to 51 ) . CONCLUSIONS Rociletinib was active in patients with EGFR-mutated NSCLC associated with the T790 M resistance mutation . ( Funded by Clovis Oncology ; Clinical Trials.gov number , NCT01526928 . )
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 .