24915778
BACKGROUND	Trametinib , an oral mitogen/extracellular signal-related kinase ( MEK ) 1/2 inhibitor , holds promise for malignancies with rat sarcoma ( RAS ) mutations , like pancreas cancer .
BACKGROUND	This phase II study was designed to determine overall survival ( OS ) in patients with pancreas cancer treated with trametinib and gemcitabine .
BACKGROUND	Secondary end-points included progression-free survival ( PFS ) , overall response rate ( ORR ) and duration of response ( DOR ) ; safety end-points were also assessed .
METHODS	Adults with untreated metastatic adenocarcinoma of the pancreas were randomised ( 1:1 ) to receive intravenous gemcitabine 1000 mg/m ( 2 ) ( weekly 7 for 8 weeks , then days 1 , 8 and 15 of 28-day cycles ) plus trametinib or placebo 2mg daily .
METHODS	RAS mutations were determined in circulating free DNA ( cfDNA ) and archival tumour tissue .
METHODS	OS was evaluated in kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutant and wild-type subgroups .
RESULTS	Baseline characteristics for 160 patients were similar in both treatment arms .
RESULTS	There was no significant difference in OS ( hazard ratio ( HR ) 0.98 ; 95 % confidence interval ( CI ) , 0.67-1 .44 ; P = .453 ) ; median OS was 8.4 months with gemcitabine plus trametinib and 6.7 months with gemcitabine plus placebo .
RESULTS	Median PFS ( 16 versus 15 weeks ) , ORR ( 22 % versus 18 % ) and median DOR ( 23.9 versus 16.1 weeks ) were also similar for trametinib and placebo arms , respectively .
RESULTS	KRAS mutation-positive patients ( n = 103 ) showed no difference in OS between arms .
RESULTS	Thrombocytopenia , diarrhoea , rash and stomatitis were more frequent with trametinib , as was grade 3 anaemia .
CONCLUSIONS	The addition of trametinib to gemcitabine did not improve OS , PFS , ORR or DOR in patients with previously untreated metastatic pancreas cancer .
CONCLUSIONS	Outcomes were independent of KRAS mutations determined by cfDNA .

