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 .
Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial.
BACKGROUND Icotinib , an oral EGFR tyrosine kinase inhibitor , had shown antitumour activity and favourable toxicity in early-phase clinical trials . We aim ed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer . METHODS In this r and omised , double-blind , phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China . Eligible patients were those aged 18 - 75 years who had not responded to one or more platinum-based chemotherapy regimen . Patients were r and omly assigned ( 1:1 ) , using minimisation methods , to receive icotinib ( 125 mg , three times per day ) or gefitinib ( 250 mg , once per day ) until disease progression or unacceptable toxicity . The primary endpoint was progression-free survival , analysed in the full analysis set . We analysed EGFR status if tissue sample s were available . All investigators , clinicians , and participants were masked to patient distribution . The non-inferiority margin was 1·14 ; non-inferiority would be established if the upper limit of the 95 % CI for the hazard ratio ( HR ) of gefitinib versus icotinib was less than this margin . This study is registered with Clinical Trials.gov , number NCT01040780 , and the Chinese Clinical Trial Registry , number ChiCTR-TRC-09000506 . FINDINGS 400 eligible patients were enrolled between Feb 26 , 2009 , and Nov 13 , 2009 ; one patient was enrolled by mistake and removed from the study , 200 were assigned to icotinib and 199 to gefitinib  . 395 patients were included in the full analysis set ( icotinib , n=199 ; gefitinib , n=196 ) . Icotinib was non-inferior to gefitinib in terms of progression-free survival ( HR 0·84 , 95 % CI 0·67 - 1·05 ; median progression-free survival 4·6 months [ 95 % CI 3·5 - 6·3 ] vs 3·4 months [ 2·3 - 3·8 ] ; p=0·13 ) . The most common adverse events were rash ( 81 [ 41 % ] of 200 patients in the icotinib group vs 98 [ 49 % ] of 199 patients in the gefitinib group ) and diarrhoea ( 43 [ 22 % ] vs 58 [ 29 % ] ) . Patients given icotinib had less drug-related adverse events than did those given gefitinib ( 121 [ 61 % ] vs 140 [ 70 % ] ; p=0·046 ) , especially drug-related diarrhoea ( 37 [ 19 % ] vs 55 [ 28 % ] ; p=0·033 ) . INTERPRETATION Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer
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 .