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 .
Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial.
BACKGROUND The results of FASTACT , a r and omised , placebo-controlled , phase 2 study , showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival ( PFS ) in patients with advanced non-small-cell lung cancer . We undertook FASTACT-2 , a phase 3 study in a similar patient population . METHODS In this phase 3 trial , patients with untreated stage IIIB/IV non-small-cell lung cancer were r and omly assigned in a 1:1 ratio by use of an interactive internet response system with minimisation algorithm ( stratified by disease stage , tumour histology , smoking status , and chemotherapy regimen ) to receive six cycles of gemcitabine ( 1250 mg/m(2 ) on days 1 and 8 , intravenously ) plus platinum ( carboplatin 5 × area under the curve or cisplatin 75 mg/m(2 ) on day 1 , intravenously ) with intercalated erlotinib ( 150 mg/day on days 15 - 28 , orally ; chemotherapy plus erlotinib ) or placebo orally ( chemotherapy plus placebo ) every 4 weeks . With the exception of an independent group responsible for monitoring data and safety monitoring board , everyone outside the interactive internet response system company was masked to treatment allocation . Patients continued to receive erlotinib or placebo until progression or unacceptable toxicity or death , and all patients in the placebo group were offered second-line erlotinib at the time of progression . The primary endpoint was PFS in the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00883779 . FINDINGS From April 29 , 2009 , to Sept 9 , 2010 , 451 patients were r and omly assigned to chemotherapy plus erlotinib ( n=226 ) or chemotherapy plus placebo ( n=225 ) . PFS was significantly prolonged with chemotherapy plus erlotinib versus chemotherapy plus placebo ( median PFS 7·6 months [ 95 % CI 7·2 - 8·3 ] , vs 6·0 months [ 5·6 - 7·1 ] , hazard ratio [ HR ] 0·57 [ 0·47 - 0·69 ] ; p<0·0001 ) . Median overall survival for patients in the chemotherapy plus erlotinib and chemotherapy plus placebo groups was 18·3 months ( 16·3 - 20·8 ) and 15·2 months ( 12·7 - 17·5 ) , respectively ( HR 0·79 [ 0·64 - 0·99 ] ; p=0·0420 ) . Treatment benefit was noted only in patients with an activating EGFR gene mutation ( median PFS 16·8 months [ 12·9 - 20·4 ] vs 6·9 months [ 5·3 - 7·6 ] , HR 0·25 [ 0·16 - 0·39 ] ; p<0·0001 ; median overall survival 31·4 months [ 22·2-undefined ] , vs 20·6 months [ 14·2 - 26·9 ] , HR 0·48 [ 0·27 - 0·84 ] ; p=0·0092 ) . Serious adverse events were reported by 76 ( 34 % ) of 222 patients in the chemotherapy plus placebo group and 69 ( 31 % ) of 226 in the chemotherapy plus erlotinib group . The most common grade 3 or greater adverse events were neutropenia ( 65 [ 29 % ] patients and 55 [ 25 % ] , respectively ) , thrombocytopenia ( 32 [ 14 % ] and 31 [ 14 % ] , respectively ) , and anaemia ( 26 [ 12 % ] and 21 [ 9 % ] , respectively ) . INTERPRETATION Intercalated chemotherapy and erlotinib is a viable first-line option for patients with non-small-cell lung cancer with EGFR mutation-positive disease or selected patients with unknown EGFR mutation status . FUNDING F Hoffmann-La Roche
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 .