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 .
Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS).
PURPOSE The results of the Iressa Pan-Asia Study ( IPASS ) , which compared gefitinib and carboplatin/paclitaxel in previously untreated never-smokers and light ex-smokers with advanced pulmonary adenocarcinoma were published previously . This report presents overall survival ( OS ) and efficacy according to epidermal growth factor receptor ( EGFR ) biomarker status . PATIENTS AND METHODS In all , 1,217 patients were r and omly assigned . Biomarkers analyzed were EGFR mutation ( amplification mutation refractory system ; 437 patients evaluable ) , EGFR gene copy number ( fluorescent in situ hybridization ; 406 patients evaluable ) , and EGFR protein expression ( immunohistochemistry ; 365 patients evaluable ) . OS analysis was performed at 78 % maturity . A Cox proportional hazards model was used to assess biomarker status by r and omly assigned treatment interactions for progression-free survival ( PFS ) and OS . RESULTS OS ( 954 deaths ) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall ( hazard ratio [ HR ] , 0.90 ; 95 % CI , 0.79 to 1.02 ; P = .109 ) or in EGFR  mutation-positive  ( HR , 1.00 ; 95 % CI , 0.76 to 1.33 ; P = .990 ) or EGFR mutation-negative  ( HR , 1.18 ; 95 % CI , 0.86 to 1.63 ; P = .309 ; treatment by EGFR mutation interaction P = .480 ) subgroups . A high proportion ( 64.3 % ) of EGFR mutation-positive patients r and omly assigned to carboplatin/paclitaxel received subsequent  EGFR tyrosine kinase inhibitors . PFS was significantly longer with gefitinib for patients whose tumors had both high EGFR gene copy number and EGFR mutation ( HR , 0.48 ; 95 % CI , 0.34 to 0.67 ) but significantly shorter when high EGFR gene copy number was not accompanied by EGFR mutation ( HR , 3.85 ; 95 % CI , 2.09 to 7.09 ) . CONCLUSION EGFR mutations are the strongest predictive biomarker for PFS and tumor response to first-line gefitinib versus carboplatin/paclitaxel . The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation ( post hoc analysis ) . Treatment-related differences observed for PFS in the EGFR mutation-positive subgroup were not apparent for OS . OS results were likely confounded by the high proportion of patients crossing over to the alternative treatment
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 .