| General information |
| Database: | DB00005 |
| Objective: | Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumabrefractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study |
| Authors: | Robert C, et al |
| Title: | Nivolumab in previously untreated melanoma without BRAF mutation. |
| Journal: | N Engl J Med |
| Year: | 2015 |
| PMID: | 25399552 |
| Trial Design |
| Clinical Trial Id: | NCT01721772 |
| Agent: | nivolumab
|
| Target: | PD1
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase III controlled study |
| Key Patients Feature: | previously untreated patients who had metastatic melanoma without a BRAF mutation |
| Biomarker: | BRAF mutation |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | dacarbazine |
| Treatment Info: | receive nivolumab (at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazinematched placebo every 3 weeks) or dacarbazine (at a dose of 1000 mg per square meter of bodysurface area every 3 weeks and nivolumabmatched placebo every 2 weeks). |
| Primary End Point: | overall survival |
| Secondary End Point: | NA |
| Patients Number: | 418 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | At 1 year, the overall rate of survival was 72.9% (95% confidence interval [CI], 65.5 to 78.9) in the nivolumab group, as compared with 42.1% (95% CI, 33.0 to 50.9) in the dacarbazine group (hazard ratio for death, 0.42; 99.79% CI, 0.25 to 0.73; P<0.001). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median progression free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group (hazard ratio for death or progression of disease, 0.43; 95% CI, 0.34 to 0.56; P<0.001). The |
| Median OS A vs. C: | At 1 year, the overall rate of survival was 72.9% (95% confidence interval [CI], 65.5 to 78.9) in the nivolumab group, as compared with 42.1% (95% CI, 33.0 to 50.9) in the dacarbazine group (hazard ratio for death, 0.42; 99.79% CI, 0.25 to 0.73; P<0.001). |
| Adverse Event(agent arm): | Common adverse events associated with nivolumab included fatigue, pruritus, and nausea. Drugrelated adverse events of grade 3 or 4 occurred in 11.7% of the patients treated with nivolumab and 17.6% of those treated with dacarbazine. |
| Conclusions: | Nivolumab was associated with significant improvements in overall survival and progression free survival, as compared with dacarbazine, among previously untreated patients who had metastatic melanoma without a BRAF mutation. |