| General information |
| Database: | DB00004 |
| Objective: | Nivolumab, a fully human IgG4 PD1 immune checkpoint inhibitor antibody, can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors. they assessed the efficacy and safety of nivolumab compared with investigator's choice of chemotherapy (ICC) as a secondline or laterline treatment in patients with advanced melanoma. |
| Authors: | theyber JS, et al |
| Title: | Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after antiCTLA4 treatment (CheckMate 037): a randomised, controlled, openlabel, phase 3 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 25795410 |
| Trial Design |
| Clinical Trial Id: | NCT01721746 |
| 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 randomised, controlled, openlabel, phase III trial |
| Key Patients Feature: | Eligible patients were 18 years or older, had unresectable or metastatic melanoma, and progressed after ipilimumab, or ipilimumab and a BRAF inhibitor if were BRAF(V 600) mutationpositive. |
| Biomarker: | BRAF(V 600) mutationpositive |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | ICC (dacarbazine 1000 mg/m(2) every 3 weeks or paclitaxel 175 mg/m(2) combined with carboplatin area under the curve 6 every 3 weeks) |
| Treatment Info: | Participating investigators randomly assigned (with an interactive voice response system) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC (dacarbazine 1000 mg/m(2) every 3 weeks or paclitaxel 175 mg/m(2) combined with carboplatin area under the curve 6 every 3 weeks) until progression or unacceptable toxic effects. |
| Primary End Point: | the proportion of patients who had an objective response and overall survival. |
| Secondary End Point: | NA |
| Patients Number: | 631 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Confirmed objective responses were reported in 38 (31.7%, 95% CI 23.540.8) of the first 120 patients in the nivolumab group versus five (10.6%, 3.523.1) of 47 patients in the ICC group. |
| Disease Control Rate: | Stable disease: 28 (23.3%) vs. 16 (34.0%) |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | median PFS was 4.7 months (95% CI 2.3-6.5) for the nivolumab group and 4.2 months (2.1-6.3) for the ICC group (hazard ratio 0.82; 99.99% CI 0.32-2.05, a descriptive comparison). 6month progression free survival was 48% (95% CI 38-56) in the nivolumab group and 34% (18-51) in the ICC group. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Grade 34 adverse events related to nivolumab included increased lipase (three [1%] of 268 patients), increased alanine aminotransferase, anaemia, and fatigue (two [1%] each); for ICC, these included neutropenia (14 [14%] of 102), thrombocytopenia (six [6%]), and anaemia (five [5%]). They noted grade 34 drugrelated serious adverse events in 12 (5%) nivolumabtreated patients and nine (9%) patients in the ICC group. No treatmentrelated deaths occurred |
| Conclusions: | Nivolumab led to a greater proportion of patients achieving an objective response and fetheyr toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor. Nivolumab represents a new treatment option with clinically meaningful durable objective responses in a population of high unmet need. |