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 .
Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial.
BACKGROUND There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung . LUX-Lung 8 compared afatinib ( an irreversible ErbB family blocker ) with erlotinib ( a reversible EGFR tyrosine kinase inhibitor ) , as second-line treatment for patients with advanced squamous cell carcinoma of the lung . METHODS We did this open-label , phase 3 r and omised controlled trial at 183 cancer centres in 23 countries worldwide . We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy .  Participants were r and omly assigned ( 1:1 ) to receive afatinib ( 40 mg per day ) or erlotinib ( 150 mg per day ) until disease progression . The r and omisation was done central ly with an interactive voice or web-based response system and stratified by ethnic origin ( eastern Asian vs non-eastern Asian ) . Clinicians and patients were not masked to treatment allocation . The primary endpoint was progression-free survival assessed by independent central review ( intention-to-treat population ) . The key secondary endpoint was overall survival . This trial is registered with Clinical Trials.gov , NCT01523587 . FINDINGS 795 eligible patients were r and omly assigned ( 398 to afatinib , 397 to erlotinib ) . Median follow-up at the time of the primary analysis of progression-free survival was 6·7 months ( IQR 3·1 - 10·2 ) , at which point enrolment was not complete . Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib ( median 2·4 months [ 95 % CI 1·9 - 2·9 ] vs 1·9 months [ 1·9 - 2·2 ] ; hazard ratio [ HR ] 0·82 [ 95 % CI 0·68 - 1·00 ] , p=0·0427 ) . At the time of the primary analysis of overall survival ( median follow-up 18·4 months [ IQR 13·8 - 22·4 ] ) , overall survival was significantly greater in the afatinib group than in the erloinib group ( median 7·9 months [ 95 % CI 7·2 - 8·7 ] vs 6·8 months [ 5·9 - 7·8 ] ; HR 0·81 [ 95 % CI 0·69 - 0·95 ] , p=0·0077 ) , as were progression-free survival ( median 2·6 months [ 95 % CI 2·0 - 2·9 ] vs 1·9 months [ 1·9 - 2·1 ] ; HR 0·81 [ 95 % CI 0·69 - 0·96 ] , p=0·0103 ) and disease control ( 201 [ 51 % ] of 398 patients vs 157 [ 40 % ] of 397 ; p=0·0020 ) . The proportion of patients with an objective response did not differ significantly between groups ( 22 [ 6 % ] vs 11 [ 3 % ] ; p=0·0551 ) . Tumour shrinkage occurred in 103 ( 26 % ) of 398 patients versus 90 ( 23 % ) of 397 patients . Adverse event profiles were similar in each group : 224 ( 57 % ) of 392 patients in the afatinib group versus 227 ( 57 % ) of 395 in the erlotinib group had grade 3 or higher adverse events . We recorded higher incidences of treatment-related grade 3 diarrhoea with afatinib ( 39 [ 10 % ] vs nine [ 2 % ] ) , of grade 3 stomatitis with afatinib ( 16 [ 4 % ] vs none ) , and of grade 3 rash or acne with erlotinib ( 23 [ 6 % ] vs 41 [ 10 % ] ) . INTERPRETATION The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib , along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung . FUNDING Boehringer Ingelheim
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 .