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 .
Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial.
BACKGROUND Necitumumab is a second-generation , recombinant , human immunoglobulin G1 EGFR antibody . In this study , we aim ed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer . METHODS We did this open-label , r and omised phase 3 study at 184 investigative sites in 26 countries . Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 - 2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion . Enrolled patients were r and omly assigned central ly 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block r and omisation scheme ( block size of four ) by a telephone-based interactive voice response system or interactive web response system . Chemotherapy was gemcitabine 1250 mg/m(2 ) administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m(2 ) administered intravenously over 120 min on day 1 of a 3-week cycle . Necitumumab 800 mg , administered intravenously over a minimum of 50 min on days 1 and 8 , was continued after the end of chemotherapy until  disease progression or intolerable toxic side-effects occurred . R and omisation was stratified by ECOG performance status and geographical region . Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash -- a class effect of EGFR antibodies -- that would have unmasked most patients and investigators to treatment . The primary endpoint was overall survival , analysed by intention to treat . We report the final clinical analysis . This study is registered with Clinical Trials.gov , number NCT00981058 . FINDINGS Between Jan 7 , 2010 , and Feb 22 , 2012 , we enrolled 1093 patients and r and omly assigned them to receive necitumumab plus gemcitabine and cisplatin ( n=545 ) or gemcitabine and cisplatin ( n=548 ) . Overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group ( median 11·5 months [ 95 % CI 10·4 - 12·6 ] ) vs 9·9 months [ 8·9 - 11·1 ] ; stratified hazard ratio 0·84 [ 95 % CI 0·74 - 0·96 ; p=0·01 ] ) . In the necitumumab plus gemcitabine and cisplatin group , the number of patients with at least one grade 3 or worse adverse event was higher ( 388 [ 72 % ] of 538 patients ) than in the gemcitabine and cisplatin group ( 333 [ 62 % ] of 541 ) , as was the incidence of serious adverse events ( 257 [ 48 % ] of 538 patients vs 203 [ 38 % ] of 541 ) . More patients in the necitumumab plus gemcitabine and cisplatin group had grade 3 - 4 hypomagnesaemia ( 47 [ 9 % ] of 538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [ 1 % ] of 541 in the gemcitabine and cisplatin group ) and grade 3 rash ( 20 [ 4 % ] vs one [ < 1 % ] ) . Including events related to disease progression , adverse events with an outcome of death were reported for 66 ( 12 % ) of 538 patients in the necitumumab plus gemcitabine and cisplatin group and 57 ( 11 % ) of 541 patients in the gemcitabine and cisplatin group ; these were deemed to be related to study drugs in 15 ( 3 % ) and ten ( 2 % ) patients , respectively . Overall , we found that the safety profile of necitumumab plus gemcitabine and cisplatin was acceptable and in line with expectations . INTERPRETATION Our findings show that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improves overall survival in patients with advanced squamous non-small-cell lung cancer and represents a new first-line treatment option for this disease . FUNDING 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 .