| General information |
| Database: | DB00003 |
| Objective: | The immune checkpoint inhibitor ipilimumab is the standardofcare treatment for patients with advanced melanoma. Pembrolizumab inhibits the programmed cell death 1 (PD1) immune checkpoint and has antitumor activity in patients with advanced melanoma. |
| Authors: | Robert C, et al |
| Title: | Pembrolizumab versus Ipilimumab in Advanced Melanoma. |
| Journal: | N Engl J Med. |
| Year: | 2015 |
| PMID: | 25891173 |
| Trial Design |
| Clinical Trial Id: | NCT01866319 |
| Agent: | pembrolizumab
|
| Target: | The antiprogrammeddeathreceptor1
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a randomized, controlled, phase III study |
| Key Patients Feature: | patients with advanced melanoma. |
| Biomarker: | BRAF V600 mutational status |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | Ipilimumab |
| Treatment Info: | assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks. |
| Primary End Point: | progression free survival and overall survival . |
| Secondary End Point: | objective response rate , the duration of response, and safety. |
| Patients Number: | 834 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The response rate was improved with pembrolizumab administered every 2 weeks (33.7%) and every 3 weeks (32.9%), as compared with ipilimumab (11.9%) (P<0.001 for both comparisons). Responses were ongoing in 89.4%, 96.7%, and 87.9% of patients, respectively, after a median followup of 7.9 months |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The estimated 6month progression freesurvival rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (hazard ratio for disease progression, 0.58; P<0.001 for both pembrolizumab regimens versus ipilimumab; 95% confidence intervals [CIs], 0.46 to 0.72 and 0.47 to 0.72, respectively). |
| Median OS A vs. C: | Estimated 12month survival rates were 74.1%, 68.4%, and 58.2%, respectively (hazard ratio for death for pembrolizumab every 2 weeks, 0.63; 95% CI, 0.47 to 0.83; P=0.0005; hazard ratio for pembrolizumab every 3 weeks, 0.69; 95% CI, 0.52 to 0.90; P=0.0036). |
| Adverse Event(agent arm): | Rates of treatmentrelated adverse events of grade 3 to 5 severity were lotheyr in the pembrolizumab groups (13.3% and 10.1%) than in the ipilimumab group (19.9%). |
| Conclusions: | The anti-PD1 antibody pembrolizumab prolonged progression free survival and overall survival and had less highgrade toxicity than did ipilimumab in patients with advanced melanoma. |