Entry Detail
| General information | |
| Database: | DB00177 |
| Objective: | Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation. |
| Authors: | Chapman PB, et al |
| Title: | Improved survival with vemurafenib in melanoma with BRAF V600E mutation. |
| Journal: | N Engl J Med. |
| Year: | 2011 |
| PMID: | 21639808 |
| Trial Design | |
| Clinical Trial Id: | NCT01006980 |
| Agent: | vemurafenib |
| Target: | BRaf protooncogene serine/threonineprotein kinase |
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced BRAF(V600E/K) mut(+) melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase III randomized clinical trial |
| Key Patients Feature: | patients with previously untreated, metastatic melanoma with the BRAF V600E mutation. |
| Biomarker: | BRAF V600E mutation |
| Biomark Analysis: | NA |
| Control Group Info: | dacarbazine |
| Treatment Info: | Patients were randomly assigned to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg per square meter of bodysurface area intravenously every 3 weeks). |
| Primary End Point: | rates of overall and progression free survival. |
| Secondary End Point: | the response rate, response duration, and safety. |
| Patients Number: | 675 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Response rates were 48% for vemurafenib and 5% for dacarbazine |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The hazard ratio for tumor progression in the vemurafenib group was 0.26 (95% CI, 0.20 to 0.33; P<0.001);the estimated median progression free survival was 5.3 months in the vemurafenib group and 1.6 months in the dacarbazine group. |
| Median OS A vs. C: | At 6 months, OS was 84% (95% [CI], 78 to 89) vs 64% (95% CI, 56 to 73) (A vs C). In the interim analysis for OS and final analysis for PFS, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). In the final analysis for OS, it reported as 13.6 vs 9.7 ms, respectively (HR 0.70, p = 0.0008)] |
| Adverse Event(agent arm): | Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamouscell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. |
| Conclusions: | Vemurafenib produced improved rates of overall and progression free survival in patients with previously untreated melanoma with the BRAF V600E mutation. |