BACKGROUND: @entity2856 ( @entity2856 ) mediates resistance to @entity470 ( @entity470 ) inhibition and may represent a therapeutic target. We conducted a multicenter, randomized, double blind, phase II/III trial of dalotuzumab, an anti- @entity2856 monoclonal antibody, with standard therapy in chemo-refractory, @entity984 wild-type metastatic @entity14 . METHODS: Eligible @entity1 were randomly assigned to dalotuzumab 10mg/kg weekly (arm A), dalotuzumab 7.5mg/kg every alternate week (arm B), or placebo (arm C) in combination with cetuximab and @entity2600 . Primary endpoints were progression-free survival (PFS) and @entity1349 ( @entity1349 ). Secondary endpoints included exploratory biomarker analyses. All statistical tests were two-sided. RESULTS: The trial was prematurely discontinued for futility after 344 eligible @entity984 wild-type @entity1 were included in the primary efficacy population (arm A = 116, arm B = 117, arm C = 111). Median PFS was 3.9 months in arm A (hazard ratio [HR] = 1.33, 95% confidence interval [CI] = 0.98 to 1.83, P = .07) and 5.4 months in arm B (HR = 1.13, 95% CI = 0.83 to 1.55, P = .44) compared with 5.6 months in arm C. Median @entity1349 was 10.8 months in arm A (HR = 1.41, 95% CI = 0.99 to 2.00, P = .06) and 11.6 months in arm B (HR = 1.26, 95% CI = 0.89 to 1.79, P = .18) compared with 14.0 months in arm C. Grade 3 or higher @entity1395 and hyperglycaemia occurred more frequently with dalotuzumab compared with placebo. In exploratory biomarker analyses, @entity1 with high @entity442 mRNA @entity5 in arm A had numerically better PFS (5.6 vs 3.6 months, HR = 0.59, 95% CI = 0.28 to 1.23, P = .16) and @entity1349 (17.9 vs 9.4 months, HR = 0.67, 95% CI = 0.31 to 1.45, P = .31) compared with those with high @entity442 mRNA @entity5 in arm C. In contrast, in arm C high @entity442 mRNA expression predicted lower response rate (17.6% vs 37.3%, P = .04), shorter PFS (3.6 vs 6.6 months, HR = 2.15, 95% CI = 1.15 to 4.02, P = .02), and shorter @entity1349 (9.4 vs 15.5 months, HR = 2.42, 95% CI = 1.21 to 4.82, P = .01). CONCLUSIONS: Adding dalotuzumab to @entity2600 and cetuximab was feasible but did not improve survival outcome. @entity2856 ligands are promising biomarkers for differential response to anti- @entity470 and anti- @entity2856 therapies.

A Randomized Phase II/III Study of Dalotuzumab in Combination With Cetuximab and XXXX in Chemorefractory, @entity984 Wild-Type, Metastatic @entity14 .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity2600 :: ('MESH:C051890', 'Chemical') :: ['irinotecan'] @entity470 :: ('1956', 'Gene') :: ['EGFR', 'epidermal growth factor receptor'] @entity984 :: ('3845', 'Gene') :: ['KRAS'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumors'] @entity442 :: ('3479', 'Gene') :: ['IGF-1'] @entity1395 :: ('MESH:D001247', 'Disease') :: ['asthenia'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer'] @entity2856 :: ('3480', 'Gene') :: ['IGF-1R', 'Insulin-like growth factor type 1 receptor'] @entity1349 :: ('MESH:D011475', 'Disease') :: ['OS', 'overall survival']
@entity2600 :: (MESH:C051890,Chemical) :: ['Irinotecan']
