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 .
EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study.
BACKGROUND Findings from the phase 3 First-Line ErbituX in lung cancer ( FLEX ) study showed that the addition of cetuximab to first-line chemotherapy significantly improved overall survival compared with chemotherapy alone ( hazard ratio [ HR ] 0·871 , 95 % CI 0·762 - 0·996 ; p=0·044 ) in patients with advanced non-small-cell lung cancer ( NSCLC ) . To define patients benefiting most from cetuximab , we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients . METHODS We used prospect ively collected tumour EGFR expression data to generate an immunohistochemistry score for FLEX study patients on a continuous scale of 0 - 300 . We used response data to select an outcome -based discriminatory threshold immunohistochemistry score for EGFR expression of 200 . Treatment outcome was analysed in patients with low ( immunohistochemistry score < 200 ) and high ( ≥200 ) tumour EGFR expression . The primary endpoint in the FLEX study was overall survival . We analysed patients from the FLEX intention-to-treat ( ITT ) population . The FLEX study is registered with Clinical Trials.gov , number NCT00148798 . FINDINGS Tumour EGFR immunohistochemistry data were available for 1121 of 1125 ( 99·6 % ) patients from the FLEX study ITT population . High EGFR expression was scored for 345 ( 31 % ) evaluable patients and low for 776 ( 69 % ) patients . For patients in the high EGFR expression group , overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group ( median 12·0 months [ 95 % CI 10·2 - 15·2 ] vs 9·6 months [ 7·6 - 10·6 ] ; HR 0·73 , 0·58 - 0·93 ; p=0·011 ) , with no meaningful increase in side-effects . We recorded no corresponding survival benefit for patients in the low EGFR expression group ( median 9·8 months [ 8·9 - 12·2 ] vs 10·3 months [ 9·2 - 11·5 ] ; HR 0·99 , 0·84 - 1·16 ; p=0·88 ) . A treatment interaction test assessing the difference in the HRs for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression ( p=0·044 ) . INTERPRETATION High EGFR expression is a tumour biomarker that can predict survival benefit from the addition of cetuximab to first-line chemotherapy in patients with advanced NSCLC . Assessment of EGFR expression could offer a personalised treatment approach in this setting . FUNDING Merck
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 .