Entry Detail
| General information | |
| Database: | DB00967 |
| Objective: | Sorafenib is an inhibitor of VEGF receptor (VEGFR), plateletderived growth factor receptor (PDGFR), and RAF kinases, amongst others. they assessed the association of somatic mutations with clinicopathologic features and clinical outcomes in patients with metastatic melanoma treated on E2603, comparing treatment with carboplatin, paclitaxel ¡À sorafenib (CP vs.CPS) |
| Authors: | Wilson MA, et al |
| Title: | Correlation of somatic mutations and clinical outcome in melanoma patients treated with Carboplatin, Paclitaxel, and sorafenib. |
| Journal: | Clin Cancer Res. |
| Year: | 2014 |
| PMID: | 24714776 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | melanoma |
| Cancer Subtype: | melanoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Carboplatin, Paclitaxel, + sorafenib |
| Study Type: | Correlation of somatic mutations and clinical outcome analysis |
| Key Patients Feature: | Pretreatment tumor samples from 179 unique individuals enrolled on E2603 were analyzed |
| Biomarker: | NRAS |
| Biomark Analysis: | A trend toward improved clinical response in patients with NRASmutant melanoma treated with CPS was observed, possibly due to the effect of sorafenib on CRAF. |
| Control Group Info: | single arm |
| Treatment Info: | Genotyping was performed using a custom iPlex panel interrogating 74 mutations in 13 genes. Statistical analysis was performed using Fisher exact test, logistic regression, and Cox proportional hazards models. progression free survival (PFS) and overall survival were estimated using KaplanMeier methods |
| Primary End Point: | Correlation of somatic mutations and clinical outcome |
| Secondary End Point: | NA |
| Patients Number: | 823 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | In patients with BRAF mutant melanoma, 15.6% and 19.2% for control and experimental arms, respectively (P=0.771); In patients with NRAS mutant melanoma, 5.6% and 22.7% for the control and experimental arms, respectively (P=0.197). In WT/WT melanoma, 16.7% and 20.0%, respectively (P>0.05). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | In patients with BRAF mutant melanoma, the median PFS was 2.2 and 5.0 months for the control and experimental arms, respectively. In patients with NRAS mutant melanoma, the median PFS was 3.0 and 5.1 months for control and experimental arms, respectively. In patients with WT/WT melanoma, 4.5 and 5.8 months for control and experimental arms, respectively, |
| Median OS A vs. C: | In patients with BRAF mutant melanoma, median OS was 8.8 and 8.9 months for control and experimental arm, respectively. In patients with NRAS mutant melanoma, the median OS was 9.8 and 10.3 months for control and experimental arms, respectively. In patients with WT/WT melanoma, median OS was 10.0 and 12.1 months for the control and experimental arms, respectively |
| Adverse Event(agent arm): | NA |
| Conclusions: | This study of somatic mutations in melanoma is the last prospectively collectedphase III clinical trial population before the era of BRAFtargeted therapy. A trend toward improved clinical response in patients with NRASmutant melanoma treated with CPS was observed, possibly due to the effect of sorafenib on CRAF |