Entry Detail
| General information | |
| Database: | DB00972 |
| Objective: | Cutaneous squamouscell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors. |
| Authors: | Su F, et al |
| Title: | RAS mutations in cutaneous squamouscell carcinomas in patients treated with BRAF inhibitors. |
| Journal: | N Engl J Med. |
| Year: | 2012 |
| PMID: | 22256804 |
| Trial Design | |
| Clinical Trial Id: | NCT00405587, NCT00949702, NCT01001299, NCT01006980 |
| Agent: | vemurafenib |
| Target: | BRaf protooncogene serine/threonineprotein kinase |
| Cancer Type: | melanoma |
| Cancer Subtype: | cutaneous squamouscell carcinomas |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a molecular analysis |
| Key Patients Feature: | patients with cutaneous squamouscell carcinomas treated with BRAF inhibitors |
| Biomarker: | oncogenic mutations (HRAS, KRAS, NRAS, CDKN2A, and TP53) |
| Biomark Analysis: | Mutations in RAS, particularly HRAS, are frequent in cutaneous squamouscell carcinomas and keratoacanthomas that develop in patients treated with vemurafenib. The molecular mechanism is consistent with the paradoxical activation of MAPK signaling and leads to accelerated growth of these lesions. |
| Control Group Info: | single arm |
| Treatment Info: | An analysis of an independent validation set and functional studies with BRAF inhibitors in the presence of the prevalent RAS mutation was also performed. |
| Primary End Point: | biomarker analysis |
| Secondary End Point: | NA |
| Patients Number: | 35 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | Mutations in RAS, particularly HRAS, are frequent in cutaneous squamouscell carcinomas and keratoacanthomas that develop in patients treated with vemurafenib. The molecular mechanism is consistent with the paradoxical activation of MAPK signaling and leads to accelerated growth of these lesions. (Funded by HoffmannLa Roche and others; ClinicalTrials.gov numbers, NCT00405587, NCT00949702, NCT01001299, and NCT01006980.). |