Entry Detail
| General information | |
| Database: | DB00174 |
| Objective: | BRAF V600 mutations occur in various nonmelanoma cancers. They undertook a histologyindependentphase 2 "basket" study of vemurafenib in BRAF V600 mutationpositive nonmelanoma cancers. |
| Authors: | Hyman DM, et al |
| Title: | Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. |
| Journal: | N Engl J Med. |
| Year: | 2015 |
| PMID: | 26287849 |
| Trial Design | |
| Clinical Trial Id: | NCT01524978 |
| Agent: | vemurafenib |
| Target: | BRaf protooncogene serine/threonineprotein kinase |
| Cancer Type: | melanoma |
| Cancer Subtype: | BRAF V600mutant nonmelanoma cancers |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a histologyindependent, flexible, earlyphase II ¡°basket¡± study |
| Key Patients Feature: | The primary end point was the response rate; secondary end points included progression free and overall survival. |
| Biomarker: | BRAF V600 mutationpositive |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutationpositive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. |
| Primary End Point: | the response rate; |
| Secondary End Point: | progression free and overall survival. |
| Patients Number: | 122 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | In the cohort with non small cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67);In the cohort with ErdheimChester disease or Langerhans'cell histiocytosis, the response rate was 43% (95% CI, 18 to 71);the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivaryduct cancer, ovarian cancer, and clearcell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | In the cohort with non small cell lung cancer, median PFS was 7.3 months (95% CI, 3.5 to 10.8). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Safety was similar to that in prior studies of vemurafenib for melanoma. |
| Conclusions: | BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non small cell lung cancer and in ErdheimChester disease and Langerhans'cell histiocytosis. The histologic context is an important determinant of response in BRAF V600mutated cancers. |