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document
Pembrolizumab versus docetaxel for previously treated , PD-L1-positive , advanced non-small-cell lung cancer ( KEYNOTE-010 ) : a randomised controlled trial . BACKGROUND Despite recent advances in the treatment of advanced non-small-cell lung cancer , there remains a need for effective treatments for progressive disease . We assessed the efficacy of pembrolizumab for patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . METHODS We did this randomised , open-label , phase 2/3 study at 202 academic medical centres in 24 countries . Patients with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1 % of tumour cells were randomly assigned ( 1:1:1 ) in blocks of six per stratum with an interactive voice-response system to receive pembrolizumab 2 mg/kg , pembrolizumab 10 mg/kg , or docetaxel 75 mg/m ( 2 ) every 3 weeks . The primary endpoints were overall survival and progression-free survival both in the total population and in patients with PD-L1 expression on at least 50 % of tumour cells . We used a threshold for significance of p < 0.00825 ( one-sided ) for the analysis of overall survival and a threshold of p < 0.001 for progression-free survival . This trial is registered at ClinicalTrials.gov , number NCT01905657 . FINDINGS Between Aug 28 , 2013 , and Feb 27 , 2015 , we enrolled 1034 patients : 345 allocated to pembrolizumab 2 mg/kg , 346 allocated to pembrolizumab 10 mg/kg , and 343 allocated to docetaxel . By Sept 30 , 2015 , 521 patients had died . In the total population , median overall survival was 10.4 months with pembrolizumab 2 mg/kg , 12.7 months with pembrolizumab 10 mg/kg , and 8.5 months with docetaxel . Overall survival was significantly longer for pembrolizumab 2 mg/kg versus docetaxel ( hazard ratio [ HR ] 0.71 , 95 % CI 0.58-0.88 ; p=0.0008 ) and for pembrolizumab 10 mg/kg versus docetaxel ( 0.61 , 0.49-0.75 ; p < 0.0001 ) . Median progression-free survival was 3.9 months with pembrolizumab 2 mg/kg , 4.0 months with pembrolizumab 10 mg/kg , and 4.0 months with docetaxel , with no significant difference for pembrolizumab 2 mg/kg versus docetaxel ( 0.88 , 0.74-1.05 ; p=0.07 ) or for pembrolizumab 10 mg/kg versus docetaxel ( HR 0.79 , 95 % CI 0.66-0.94 ; p=0.004 ) . Among patients with at least 50 % of tumour cells expressing PD-L1 , overall survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 14.9 months vs 8.2 months ; HR 0.54 , 95 % CI 0.38-0.77 ; p=0.0002 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 17.3 months vs 8.2 months ; 0.50 , 0.36-0.70 ; p < 0.0001 ) . Likewise , for this patient population , progression-free survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 5.0 months vs 4.1 months ; HR 0.59 , 95 % CI 0.44-0.78 ; p=0.0001 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 5.2 months vs 4.1 months ; 0.59 , 0.45-0.78 ; p < 0.0001 ) . Grade 3-5 treatment-related adverse events were less common with pembrolizumab than with docetaxel ( 43 [ 13 % ] of 339 patients given 2 mg/kg , 55 [ 16 % ] of 343 given 10 mg/kg , and 109 [ 35 % ] of 309 given docetaxel ) . INTERPRETATION Pembrolizumab prolongs overall survival and has a favourable benefit-to-risk profile in patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . These data establish pembrolizumab as a new treatment option for this population and validate the use of PD-L1 selection . FUNDING Merck & Co .
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Intervention_Pharmacological
Pembrolizumab
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Intervention_Pharmacological
docetaxel
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Intervention_Pharmacological
pembrolizumab
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Intervention_Pharmacological
pembrolizumab
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Intervention_Pharmacological
pembrolizumab
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Intervention_Pharmacological
docetaxel
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Intervention_Pharmacological
pembrolizumab
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Intervention_Pharmacological
docetaxel
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Intervention_Pharmacological
pembrolizumab
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Intervention_Pharmacological
pembrolizumab
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Intervention_Pharmacological
docetaxel
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Intervention_Pharmacological
pembrolizumab
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Intervention_Pharmacological
pembrolizumab
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Intervention_Pharmacological
pembrolizumab
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Intervention_Pharmacological
pembrolizumab
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Intervention_Pharmacological
docetaxel
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Intervention_Pharmacological
pembrolizumab
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Intervention_Pharmacological
docetaxel
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Intervention_Pharmacological
Pembrolizumab
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Intervention_Pharmacological
pembrolizumab
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Outcome_Mortality
survival and progression-free survival
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Outcome_Mortality
median overall survival
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Outcome_Mortality
Overall survival
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Outcome_Mortality
Median progression-free survival
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Outcome_Mortality
overall survival
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Outcome_Mortality
progression-free survival
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Outcome_Adverse-effects
Grade 3-5 treatment-related adverse events
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Outcome_Mortality
overall survival
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Participant_Condition
previously treated , PD-L1-positive , advanced non-small-cell lung cancer
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Participant_Condition
advanced non-small-cell lung cancer
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Participant_Condition
previously treated , PD-L1-positive , advanced non-small-cell lung cancer
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Participant_Condition
Patients with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1 % of tumour cells
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Participant_Sample-size
1034 patients