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 pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study.
BACKGROUND Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits lig and binding . We aim ed to compare necitumumab plus pemetrexed and cisplatin with pemetrexed and cisplatin alone in patients with previously untreated , stage IV , non-squamous non-small-cell lung cancer ( NSCLC ) . METHODS We did this r and omised , open-label , controlled phase 3 study at 103 sites in 20 countries . Patients aged 18 years or older , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 - 2 and adequate organ function , were r and omly assigned 1:1 to treatment with a block r and omisation scheme ( block size of four ) via a telephone-based interactive voice-response system or interactive web-response system . Patients received either cisplatin 75 mg/m(2 ) and pemetrexed 500 mg/m(2 ) on day 1 of a 3-week cycle for a maximum of six cycles alone , or with necitumumab 800 mg on days 1 and 8 . Necitumumab was continued after the end of chemotherapy until disease progression or unacceptable toxic effects . R and omisation was stratified by smoking history , ECOG performance status , disease histology , and geographical region . Patients and study investigators were not masked to group assignment . The primary endpoint was overall survival . Efficacy analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00982111 . FINDINGS Between Nov 11 , 2009 , and Feb 2 , 2011 , we r and omly assigned 633 patients to receive either necitumumab plus pemetrexed and cisplatin ( n=315 ) or pemetrexed and cisplatin alone ( n=318 ) . Enrolment was stopped on Feb 2 , 2011 , after a recommendation from the independent data monitoring committee . There was no significant difference in overall survival between treatment groups , with a median overall survival of 11·3 months ( 95 % CI 9·5 - 13·4 ) in the necitumumab plus pemetrexed and cisplatin group versus 11·5 months ( 10·1 - 13·1 ) in the pemetrexed and cisplatin group ( hazard ratio 1·01 [ 95 % CI 0·84 - 1·21 ] ; p=0·96 ) . The incidence of grade 3 or worse adverse events , including deaths , was higher in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group ; in particular , deaths regarded as related to study drug were reported in 15 ( 5 % ) of 304 patients in the necitumumab group versus nine ( 3 % ) of 312 patients in the pemetrexed and cisplatin group . Serious adverse events were likewise more frequent in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group ( 155 [ 51 % ] of 304 vs 127 [ 41 % ] of 312 patients ) . Patients in the necitumumab plus pemetrexed and cisplatin group had more grade 3 - 4 rash ( 45 [ 15 % ] of 304 vs one [ < 1 % ] of 312 patients in the pemetrexed and cisplatin alone group ) , hypomagnesaemia ( 23 [ 8 % ] vs seven [ 2 % ] patients ) , and grade 3 or higher venous thromboembolic events ( 23 [ 8 % ] vs 11 [ 4 % ] patients ) than did those in the pemetrexed and cisplatin alone group . INTERPRETATION Our findings show no evidence to suggest that the addition of necitumumab to pemetrexed and cisplatin increases survival of previously untreated patients with stage IV non-squamous NSCLC . Unless future studies identify potentially useful predictive biomarkers , necitumumab is unlikely to provide benefit in this patient population when combined with pemetrexed and cisplatin . 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 .