Entry Detail
| General information | |
| Database: | DB00178 |
| Objective: | Approximately 50% of melanomas harbor activating (V600) mutations in the serinethreonine protein kinase BRAF (BRAF). The oral BRAF inhibitor vemurafenib (PLX4032) frequently produced tumor regressions in patients with BRAF V600mutant metastatic melanoma in a phase 1 trial and improved overall survival in a phase 3 trial. |
| Authors: | Sosman JA, et al |
| Title: | Survival in BRAF V600mutant advanced melanoma treated with vemurafenib |
| Journal: | N Engl J Med. |
| Year: | 2012 |
| PMID: | 22356324 |
| 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 multicenterphase II trial |
| Key Patients Feature: | patients with previously treated BRAF V600mutant metastatic melanoma |
| Biomarker: | BRAF V600mutant |
| Biomark Analysis: | Vemurafenib induces clinical responses in more than half of patients with previously treated BRAF V600mutant metastatic melanoma |
| Control Group Info: | single arm |
| Treatment Info: | Patients received vemurafenib at a dose of 960 mg orally twice daily until the development of unacceptable toxic effects or disease progression |
| Primary End Point: | to investigate the efficacy of vemurafenib with respect to overall response rate, duration of response, and overall survival. |
| Secondary End Point: | the overall response rate; OS. |
| Patients Number: | 132 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | The confirmed overall response rate was 53% (95% confidence interval [CI], 44 to 62; 6% with a complete response and 47% with a partial response), the median duration of response was 6.7 months (95% CI, 5.6 to 8.6); Primary progression was observed in only 14% of patients. Some patients had a response after receiving vemurafenib for more than 6 months. |
| Disease Control Rate: | as the former |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | median progression free survival was 6.8 months (95% CI, 5.6 to 8.1). |
| Median OS A vs. C: | The median overall survival was 15.9 months (95% CI, 11.6 to 18.3). |
| Adverse Event(agent arm): | The most common adverse events were grade 1 or 2 arthralgia, rash, photosensitivity, fatigue, and alopecia. Cutaneous squamouscell carcinomas (the majority, keratoacanthoma type) were diagnosed in 26% of patients. |
| Conclusions: | Vemurafenib induces clinical responses in more than half of patients with previously treated BRAF V600mutant metastatic melanoma. In this study with a long followup, the median overall survival was approximately 16 months. |