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 .
Docetaxel or pemetrexed with or without cetuximab in recurrent or progressive non-small-cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial.
BACKGROUND Available pre clinical and phase 2 clinical data suggest that the addition of cetuximab , a monoclonal antibody directed against the epidermal growth factor receptor ( EGFR ) , to chemotherapy might improve outcome in patients with advanced non-small-cell lung cancer ( NSCLC ) . We aim ed to assess whether the addition of cetuximab to chemotherapy improved progression-free survival in patients with recurrent or progressive NSCLC after platinum-based therapy . METHODS In this unmasked , open-label r and omised phase 3 trial we enrolled patients with metastatic , unresectable , or locally advanced NSCLC from 121 sites in Canada and the USA . Eligible patients were those aged 18 years or older who had experienced progressive disease during or after one previous platinum-based regimen . Initially , patients were r and omly assigned to receive either pemetrexed ( 500 mg/m(2 ) ) or docetaxel ( 75 mg/m(2 ) ) and then r and omly assigned within each group to receive their chemotherapy with or without cetuximab ( 400 mg/m(2 ) at first dose and 250 mg/m(2 ) weekly thereafter ) until disease progression or unacceptable toxicity . However , after a change in the st and ard of care , investigators chose whether to treat with pemetrexed or docetaxel on a patient-by-patient basis . The primary analysis was changed to compare progression-free survival with cetuximab plus pemetrexed versus pemetrexed , on an intention-to-treat basis . This study is registered with Clinical Trials.gov , number NCT00095199 . FINDINGS Between Jan 10 , 2005 , and Feb 10 , 2010 , we enrolled 939 patients ; data for one patient was accidentally discarded . Of the remaining 938 patients , 605 received pemetrexed ( 301 patients with cetuximab and 304 alone ) and 333 received docetaxel ( 167 in combination with cetuximab and 166 alone ) . Median progression-free survival  with cetuximab plus pemetrexed was 2·9 months ( 95 % CI 2·7 - 3·2 ) versus 2·8 months ( 2·5 - 3·3 ) with pemetrexed ( HR 1·03 , 95 % CI 0·87 - 1·21 ; p=0·76 ) . The most common grade 3 - 4 adverse events  with cetuximab plus pemetrexed  were fatigue ( 33 [ 11 % ] of 292 patients ) , acneiform rash ( 31 [ 11 % ] ) , dyspnoea ( 29 [ 10 % ] ) , and decreased neutrophil count ( 28 [ 10 % ] ) , and with pemetrexed alone were dyspnoea ( 35 [ 12 % ] of 289 patients ) , decreased neutrophil count ( 26 [ 9 % ] ) , and fatigue ( 23 [ 8 % ] ) . A significantly higher proportion of patients in the cetuximab plus pemetrexed group ( 119 [ 41 % ] of 292 patients ) experienced at least one serious adverse event than those patients in the pemetrexed group ( 85 [ 29 % ] of 289 patients ; p=0·0054 ) . Nine ( 3 % ) of 292 treated patients in the cetuximab and pemetrexed group died of adverse events compared with five ( 2 % ) of 289 treated patients in the pemetrexed alone group . INTERPRETATION The use of cetuximab is not recommended in combination with chemotherapy in patients previously treated with platinum-based therapy . FUNDING Eli Lilly and Company and ImClone Systems LLC , a wholly owned subsidiary of Eli Lilly and Company
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 .