Nivolumab in Previously Untreated Melanoma without a BRAF mutation

Robert, Caroline, Long, Georgina, Brady, Benjamin, Dutriaux, Caroline, Miao, Michele, Mortier, Laurent, Hassel, Jessica C., Rutkowski, Piotr, McNeil, Catriona, Kalinsk-Warzocha, Ewa, Savage, Kerry, Hernberg, Michaela, Lebbe, Cleste, Charles, Julie, Mihalcioiu, Caitlin, Chiarion-Sileni, Vanna, Mauch, Conrelia, Cognetti, Francesco, Arance, Ana, Schmidt, Kenrik, Schadendorf, Dirk, Gogas, Helen, Lundgren-Erikkson, Lotta, Horak, Christine, Sharkey, Brian, Waxman, Ian, Atkinson, Victoria and Ascierto, Paolo (2015) Nivolumab in Previously Untreated Melanoma without a BRAF mutation. The New England Journal of Medicine, 372 4: 320-330. doi:10.1056/NEJMoa1412082

Author Robert, Caroline
Long, Georgina
Brady, Benjamin
Dutriaux, Caroline
Miao, Michele
Mortier, Laurent
Hassel, Jessica C.
Rutkowski, Piotr
McNeil, Catriona
Kalinsk-Warzocha, Ewa
Savage, Kerry
Hernberg, Michaela
Lebbe, Cleste
Charles, Julie
Mihalcioiu, Caitlin
Chiarion-Sileni, Vanna
Mauch, Conrelia
Cognetti, Francesco
Arance, Ana
Schmidt, Kenrik
Schadendorf, Dirk
Gogas, Helen
Lundgren-Erikkson, Lotta
Horak, Christine
Sharkey, Brian
Waxman, Ian
Atkinson, Victoria
Ascierto, Paolo
Title Nivolumab in Previously Untreated Melanoma without a BRAF mutation
Journal name The New England Journal of Medicine   Check publisher's open access policy
ISSN 0028-4793
Publication date 2015-01-01
Year available 2015
Sub-type Article (original research)
DOI 10.1056/NEJMoa1412082
Open Access Status DOI
Volume 372
Issue 4
Start page 320
End page 330
Total pages 11
Place of publication Waltham, MA United States
Publisher Massachusetts Medical Society
Language eng
Formatted abstract
Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study.

We randomly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab (at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks) or dacarbazine (at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks). The primary end point was overall survival.

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). 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 objective response rate was 40.0% (95% CI, 33.3 to 47.0) in the nivolumab group versus 13.9% (95% CI, 9.5 to 19.4) in the dacarbazine group (odds ratio, 4.06; P<0.001). The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups, including subgroups defined by status regarding the programmed death ligand 1 (PD-L1). Common adverse events associated with nivolumab included fatigue, pruritus, and nausea. Drug-related 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.

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
Keyword Nivolumab
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 1507 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 1463 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 22 Jul 2015, 03:16:02 EST by Victoria Atkinson on behalf of Medicine - Princess Alexandra Hospital