| General information |
| Database: | DB00996 |
| Objective: | Insulinlike growth factor type 1 receptor (IGF1R) mediates resistance to epidermal growth factor receptor (EGFR) inhibition and may represent a therapeutic target. they conducted a multicenter, randomized, double blind, phase II/III trial of dalotuzumab, an antiIGF1R monoclonal antibody, with standard therapy in chemorefractory, KRAS wildtype metastatic colorectal cancer. |
| Authors: | Sclafani F, et al |
| Title: | A Randomizedphase II/III Study of Dalotuzumab in Combination With Cetuximab and Irinotecan in Chemorefractory, KRAS WildType, Metastatic Colorectal Cancer. |
| Journal: | J Natl Cancer Inst. |
| Year: | 2015 |
| PMID: | 26405092 |
| Trial Design |
| Clinical Trial Id: | NCT00614393 |
| Agent: | Dalotuzumab Cetuximab
|
| Target: | NA
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Dalotuzumab+ Cetuximab+ Irinotecan |
| Study Type: | A Randomizedphase II/III Study |
| Key Patients Feature: | pts with Chemorefractory, KRAS WildType, Metastatic Colorectal Cancer |
| Biomarker: | IGF1 mRNA expression |
| Biomark Analysis: | In exploratory biomarker analyses, patients with high IGF1 mRNA tumors 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 OS (17.9 vs 9.4 months, HR = 0.67, 95% CI = 0.31 to 1.45, P = .31) compared with those with high IGF1 mRNA tumors in arm C. In contrast, in arm C high IGF1 mRNA expression predicted lotheyr 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 OS (9.4 vs 15.5 months, HR = 2.42, 95% CI = 1.21 to 4.82, P = .01). |
| Control Group Info: | dalotuzumab 10mg/kg weekly (arm A), dalotuzumab 7.5mg/kg every alternate week (arm B), or placebo (arm C) in combination with cetuximab and irinotecan. |
| Treatment Info: | Eligible patients 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 irinotecan. |
| Primary End Point: | progression free survival (PFS) and overall survival (OS). |
| Secondary End Point: | exploratory biomarker analyses. |
| Patients Number: | 344 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 21.6%, 23.9%, and 26.1% of patients in arms A, B, and C, respectively |
| Disease Control Rate: | in arm A was statistically significantly lotheyr compared with the control arm (42.3% vs 65.7%) |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 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 OS A vs. C: | 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. |
| Adverse Event(agent arm): | Grade 3 or higher hyperglycaemia was more frequently observed in arm A (21.0%, P < .01) and B (17.6%, P < .01) vs in arm C (5.2%), and a higher number of patients in arm B experienced grade 3 or higher asthenia (9.2%) compared with the control arm |
| Conclusions: | Adding dalotuzumab to irinotecan and cetuximab was feasible but did not improve survival outcome. IGF1R ligands are promising biomarkers for differential response to antiEGFR and antiIGF1R therapies. |