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Nivolumab in Previously Untreated Melanoma without BRAF Mutation

Robert, Caroline; Long, Georgina V.; Brady, Benjamin; Dutriaux, Caroline; Maio, Michele; Mortier, Laurent; Hassel, Jessica C.; Rutkowski, Piotr; McNeil, Catriona and Kalinka-Warzocha, Ewa, et al. (2015) In New England Journal of Medicine 372(4). p.320-330
Abstract
BACKGROUND 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. METHODS 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. RESULTS At 1 year,... (More)
BACKGROUND 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. METHODS 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. RESULTS 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. 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. (Less)
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New England Journal of Medicine
volume
372
issue
4
pages
320 - 330
publisher
Massachusetts Medical Society
external identifiers
  • wos:000348204500007
  • scopus:84925222119
ISSN
0028-4793
DOI
10.1056/NEJMoa1412082
language
English
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yes
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18c3c09f-c753-4a39-8da5-b5698c93b8b6 (old id 5190601)
date added to LUP
2015-04-01 07:38:49
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2017-11-19 03:12:23
@article{18c3c09f-c753-4a39-8da5-b5698c93b8b6,
  abstract     = {BACKGROUND 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. METHODS 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. RESULTS 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 &lt; 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 &lt; 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 &lt; 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. 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.},
  author       = {Robert, Caroline and Long, Georgina V. and Brady, Benjamin and Dutriaux, Caroline and Maio, Michele and Mortier, Laurent and Hassel, Jessica C. and Rutkowski, Piotr and McNeil, Catriona and Kalinka-Warzocha, Ewa and Savage, Kerry J. and Hernberg, Micaela M. and Lebbe, Celeste and Charles, Julie and Mihalcioiu, Catalin and Chiarion-Sileni, Vanna and Mauch, Cornelia and Cognetti, Francesco and Arance, Ana and Schmidt, Henrik and Schadendorf, Dirk and Gogas, Helen and Lundgren, Lotta and Horak, Christine and Sharkey, Brian and Waxman, Ian M. and Atkinson, Victoria and Ascierto, Paolo A.},
  issn         = {0028-4793},
  language     = {eng},
  number       = {4},
  pages        = {320--330},
  publisher    = {Massachusetts Medical Society},
  series       = {New England Journal of Medicine},
  title        = {Nivolumab in Previously Untreated Melanoma without BRAF Mutation},
  url          = {http://dx.doi.org/10.1056/NEJMoa1412082},
  volume       = {372},
  year         = {2015},
}