BACKGROUND: Optimum management strategies for @entity1 with advanced @entity1149 ( @entity1149 ) with acquired resistance to @entity470 @entity4149 -kinase inhibitors are undefined. We aimed to assess the efficacy and safety of continuing @entity4562 combined with chemotherapy versus chemotherapy alone in @entity1 with @entity470 -mutation-positive advanced @entity1149 with acquired resistance to first-line @entity4562 . METHODS: The randomised, phase 3, multicentre IMPRESS study was done in 71 centres in 11 countries in Europe and the Asia-Pacific region. Eligible @entity1 were aged at least 18 years with histologically confirmed, chemotherapy-naive, stage IIIB-IV @entity470 -mutation-positive advanced @entity1149 with previous disease control with first-line @entity4562 and recent disease progression (Response Evaluation Criteria in Solid Tumors version 1.1). @entity1 were randomly assigned (1:1) by central block randomisation to oral @entity4562 250 mg or placebo once daily in tablet form; randomisation did not include stratification factors. All @entity1 also received the @entity902 -based doublet chemotherapy @entity900 75 mg/m(2) plus pemetrexed 500 mg/m(2) on the first day of each cycle. After completion of a maximum of six chemotherapy cycles, @entity1 continued their randomly assigned treatment until disease progression or another discontinuation criterion was met. All study investigators and @entity1 were masked to treatment allocation. The primary endpoint was progression-free survival in the intention-to-treat population. Safety was assessed in @entity1 who received at least one dose of study treatment. The study has completed enrolment, but @entity1 are still in follow-up for overall survival. This trial is registered with ClinicalTrials.gov, number NCT01544179. FINDINGS: Between March 29, 2012, and Dec 20, 2013, 265 @entity1 were randomly assigned: 133 to the @entity4562 group and 132 to the placebo group. At the time of data cutoff (May 5, 2014), 98 (74%) @entity1 had disease progression in the @entity4562 group compared with 107 (81%) in the placebo group (hazard ratio 0  86, 95% CI 0  65-1  13; p=0  27; median progression-free survival 5  4 months in both groups [95% CI 4  5-5  7 in the @entity4562 group and 4  6-5  5 in the placebo group]). The most common adverse events of any grade were @entity390 (85 [64%] of 132 @entity1 in the @entity4562 group and 81 [61%] of 132 @entity1 in the placebo group) and decreased appetite (65 [49%] and 45 [34%]). The most common adverse events of grade 3 or worse were @entity417 (11 [8%] of 132 @entity1 in the @entity4562 group and five [4%] of 132 @entity1 in the placebo group) and @entity1398 (nine [7%] and seven [5%]). 37 (28%) of 132 @entity1 in the @entity4562 group and 28 (21%) of 132 @entity1 in the placebo group reported serious adverse events. INTERPRETATION: Continuation of @entity4562 after radiological disease progression on first-line @entity4562 did not prolong progression-free survival in @entity1 who received @entity902 -based doublet chemotherapy as subsequent line of treatment. @entity902 -based doublet chemotherapy remains the standard of care in this setting. FUNDING: AstraZeneca.

@entity4562 plus chemotherapy versus placebo plus chemotherapy in @entity470 -mutation-positive @entity1149 after progression on first-line XXXX (IMPRESS): a phase 3 randomised trial.

@entity1 :: ('9606', 'Species') :: ['participants', 'patients', 'Participants'] @entity390 :: ('MESH:D009325', 'Disease') :: ['nausea'] @entity4562 :: ('MESH:C419708', 'Chemical') :: ['gefitinib'] @entity417 :: ('MESH:D000740', 'Disease') :: ['anaemia'] @entity470 :: ('1956', 'Gene') :: ['EGFR'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small-cell lung cancer'] @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['neutropenia'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine'] @entity902 :: ('MESH:D010984', 'Chemical') :: ['Platinum', 'platinum']
@entity4562 :: (MESH:C419708,Chemical) :: ['gefitinib']
