Entry Detail
| General information | |
| Database: | DB00195 |
| Objective: | Some melanomas arising from acral, mucosal, and chronically sundamaged sites harbor activating mutations and amplification of the type III transmembrane receptor tyrosine kinase KIT. They explored the effects of KIT inhibition using imatinib mesylate in this molecular subset of disease.To assess clinical effects of imatinib mesylate in patients with melanoma harboring KIT alterations |
| Authors: | Carvajal RD, et al |
| Title: | KIT as a therapeutic target in metastatic melanoma. |
| Journal: | JAMA. |
| Year: | 2011 |
| PMID: | 21642685 |
| Trial Design | |
| Clinical Trial Id: | NCT00470470 |
| Agent: | imatinib mesylate |
| Target: | Abl Plateletderived growth factor receptor Mast/stem cell growth factor receptor |
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | A singlegroup, openlabel, phase II trial |
| Key Patients Feature: | patients with melanoma screened for the presence of KIT mutations and amplification at 1 community and 5 academic oncology centers in the United States |
| Biomarker: | the presence of KIT mutations and amplification; |
| Biomark Analysis: | Response rate was better in cases with mutations affecting recurrent hotspots or with a mutant to wildtype allelic ratio of more than 1 (40% vs 0%, P = .05), indicating positive selection for the mutated allele |
| Control Group Info: | single arm |
| Treatment Info: | Imatinib mesylate, 400 mg orally twice daily. |
| Primary End Point: | Radiographic response |
| Secondary End Point: | time to progression, overall survival, and correlation of molecular alterations and clinical response. |
| Patients Number: | 295 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Two complete responses lasting 94 (ongoing) and 95 weeks, 2 durable partial responses lasting 53 and 89 (ongoing) weeks, and 2 transient partial responses lasting 12 and 18 weeks among the 25 evaluable patients were observed. The overall durable response rate was 16% (95% confidence interval [CI], 2%30%), |
| Disease Control Rate: | not mentioned |
| Median Time to Progression: | with a median time to progression of 12 weeks (interquartile range [IQR], 618 weeks; 95% CI, 1118 weeks), |
| Median PFS A vs. C: | not mentioned |
| Median OS A vs. C: | a median overall survival of 46.3 weeks (IQR, 28 weeksnot achieved; 95% CI, 28 weeksnot achieved). |
| Adverse Event(agent arm): | not mentioned |
| Conclusions: | Among patients with advanced melanoma harboring KIT alterations, treatment with imatinib mesylate results in significant clinical responses in a subset of patients. Responses may be limited to tumors harboring KIT alterations of proven functional relevance. |