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 .
Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial.
BACKGROUND Patients with advanced non-squamous non-small-cell lung cancer ( NSCLC ) benefit from pemetrexed maintenance therapy after induction therapy with a platinum-containing , non-pemetrexed doublet . The PARAMOUNT trial investigated whether continuation maintenance with pemetrexed improved progression-free survival after induction therapy with pemetrexed plus cisplatin . METHODS In this double-blind , multicentre , phase 3 , r and omised placebo-controlled trial , patients with advanced non-squamous NSCLC aged 18 years or older , with no previous systemic chemotherapy for lung cancer , with at least one measurable lesion , and an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 or 1 participated . Before r and omisation , patients entered an induction phase which consisted of four cycles of induction pemetrexed ( 500 mg/m(2 ) ) plus cisplatin ( 75 mg/m(2 ) ) on day 1 of a 21-day cycle . Patients who did not progress after completion of four cycles of induction and who had an ECOG performance status of 0 or 1 were stratified according to disease stage ( IIIB or IV ) , ECOG performance status ( 0 or 1 ) , and induction response ( complete or partial response , or stable disease ) , and r and omly assigned ( 2:1 ratio ) to receive maintenance therapy with either pemetrexed ( 500 mg/m(2 ) every 21 days ) plus best supportive care or placebo plus best supportive care until disease progression . R and omisation was done with the Pocock and Simon minimisation method . Patients and investigators were masked to treatment assignment . The primary endpoint was progression-free survival in the intention-to-treat population . This study is registered with Clinical Trials.gov , NCT00789373 . FINDINGS Of the 1022 patients enrolled , 939 participated in the induction phase . Of these , 539 patients were r and omly assigned to receive continuation maintenance with pemetrexed plus best supportive care ( n=359 ) or with placebo plus best supportive care ( n=180 ) . Among the 359 patients r and omised to continuation maintenance with pemetrexed , there was a significant reduction in the risk of disease progression over the placebo group ( HR 0·62 , 95 % CI 0·49 - 0·79 ; p<0·0001 ) . The median progression-free survival , measured from r and omisation , was 4·1 months ( 95 % CI 3·2 - 4·6 ) for pemetrexed and 2·8 months ( 2·6 - 3·1 ) for placebo . Possibly treatment-related laboratory grade 3 - 4 adverse events were more common in the pemetrexed group ( 33 [ 9 % ] of 359 patients ) than in the placebo group ( one [ < 1 % ] of 180 patients ; p<0·0001 ) , as were non-laboratory grade 3 - 5 adverse events ( 32 [ 9 % ] of 359 patients in the pemetrexed group ; eight [ 4 % ] of 180 patients in the placebo group ; p=0·080 ) ; one possibly treatment-related death was reported in each group . The most common adverse events of grade 3 - 4 in the pemetrexed group were anaemia ( 16 [ 4 % ] of 359 patients ) , neutropenia ( 13 [ 4 % ] ) , and fatigue ( 15 [ 4 % ] ) . In the placebo group , these adverse events were less common : anaemia ( one [ < 1 % ] of 180 patients ) , neutropenia ( none ) , and fatigue ( one < 1 % ] ) . The most frequent serious adverse events were anaemia ( eight [ 2 % ] of 359 patients in the pemetrexed group vs none in the placebo group ) and febrile neutropenia ( five [ 1 % ] vs none ) . Discontinuations due to drug-related adverse events occurred in 19 ( 5 % ) patients in the pemetrexed group and six ( 3 % ) patients in the placebo group . INTERPRETATION Continuation maintenance with pemetrexed is an effective and well tolerated treatment option for patients with advanced non-squamous NSCLC with good performance status who have not progressed after induction therapy with pemetrexed plus 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 .