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 .
Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study.
BACKGROUND Erlotinib , docetaxel , and pemetrexed are approved for the second-line treatment of non-small-cell lung cancer ( NSCLC ) , but no head-to-head data from large clinical trials are available . We undertook the Tarceva In Treatment of Advanced NSCLC ( TITAN ) study to assess the efficacy and tolerability of second-line erlotinib versus chemotherapy in patients with refractory NSCLC . METHODS TITAN was an international , r and omised multicentre , open-label , phase 3 study that was done at 77 sites in 24 countries . Chemotherapy-naive patients with locally advanced , recurrent , or metastatic NSCLC received up to four cycles of first-line platinum doublet chemotherapy , after which patients with disease progression during or immediately after chemotherapy were offered enrolment into TITAN . Enrolled patients were r and omly assigned ( 1:1 ) by a minimisation method to ensure balanced stratification , to receive erlotinib 150 mg/day or chemotherapy ( st and ard docetaxel or pemetrexed regimens , at the treating investigators ' discretion ) , until unacceptable toxicity , disease progression , or death . Patients were stratified by disease stage , Eastern Cooperative Oncology Group performance status , smoking history , and region of residence . The primary endpoint was overall survival in the intention-to-treat population . TITAN was halted prematurely because of slow recruitment . This study is registered with Clinical Trials.gov , number NCT00556322 . FINDINGS Between April 10 , 2006 , and Feb 24 , 2010 , 2590 chemotherapy-naive patients were treated with first-line platinum doublet chemotherapy , of whom 424 had disease progression and were enrolled into TITAN . 203 patients were r and omly assigned to receive erlotinib and 221 were assigned to receive chemotherapy .  Median follow-up was 27·9 months ( IQR 11·0 - 36·0 ) in the erlotinib group and 24·8 months ( 12·1 - 41·6 ) in the chemotherapy  group . Median overall survival was 5·3 months ( 95 % CI 4·0 - 6·0 ) with erlotinib and 5·5 months ( 4·4 - 7·1 ) with chemotherapy ( hazard ratio [ HR ] 0·96 , 95 % CI 0·78 - 1·19 ; log-rank p=0·73 ) . The adverse-event profile of each group was in line with previous studies . Rash ( 98/196 [ 50 % ] in the erlotinib group vs 10/213 [ 5 % ] in the chemotherapy group for all grade s ; nine [ 5 % ] vs none for grade 3 or 4 ) and diarrhoea ( 36 [ 18 % ] vs four [ 2 % ] for all grade s ; five [ 3 % ] vs none for grade 3 or 4 ) were the most common treatment-related adverse events with erlotinib , whereas alopecia ( none vs 23 [ 11 % ] for all grade s ; none vs one [ < 1 % ] for grade 3/4 ) was the most common treatment-related adverse event with chemotherapy . INTERPRETATION No significant differences in efficacy were noted between patients treated with erlotinib and those treated with docetaxel or pemetrexed . Since the toxicity profiles of erlotinib and chemotherapy differ , second-line treatment decisions should take into account patient preference and specific toxicity risk profiles . 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 .