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JAMA Oncol. 2018 Oct 25. doi: 10.1001/jamaoncol.2018.4514. [Epub ahead of print]

Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial.

Author information

1
Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
2
Melanoma Institute Australia, Sydney, New South Wales, Australia.
3
Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
4
Department of Medical Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales, Australia.
5
Department of Medicine, Institute Gustave Roussy, Villejuif, France.
6
Medical Oncology and Haematology, Cabrini Health, Melbourne, Victoria, Australia.
7
Dermatology Service, University Hospital of Bordeaux, Bordeaux, France.
8
UOC Oncological Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.
9
Clinique de Dermatologie, Unité d'Onco-Dermatologie, Institut National de la Santé et de la Recherche Médicale (INSERM) U1189, Centre Hospitalier Régional Universitaire de Lille, Lille, France.
10
Department of Dermatology, University Hospital Heidelberg and National Center for Tumor Diseases, Heidelberg, Germany.
11
Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Institute-Oncology Center, Warsaw, Poland.
12
Chris O'Brien Lifehouse, Melanoma Institute Australia, Camperdown, New South Wales.
13
Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
14
Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.
15
Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
16
Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
17
Assistance Publique-Hôpitaux de Paris Dermatology and Centre d'Investigation Clinique, University Paris Diderot INSERM U976, Saint Louis Hospital, Paris, France.
18
Institute for Advanced Biosciences, Université Grenoble Alpes/INSERM U1209/CNRS UMR 5309 Joint Research Center, Grenoble, France.
19
Dermatology Department, Grenoble Alpes University Hospital, Grenoble, France.
20
Department of Oncology, McGill University, Montreal, Quebec, Canada.
21
Melanoma Cancer Unit, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua, Italy.
22
Department of Dermatology, University Hospital Cologne, Cologne, Germany.
23
Division of Oncology, Regina Elena Institute, Rome, Italy.
24
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
25
Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
26
Center for Cancer Immune Therapy, Herlev Hospital, Herlev, Denmark.
27
Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
28
Department of Dermatology, University Hospital Essen, Essen, Germany.
29
German Cancer Consortium, Heidelberg, Germany.
30
First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
31
Global Biometric Sciences, Bristol-Myers Squibb, Princeton, New Jersey.
32
Oncology Clinical Development, Bristol-Myers Squibb, Princeton, New Jersey.
33
Princess Alexandra Hospital, University of Queensland, Woolloongabba, Queensland, Australia.
34
Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Greenslopes, Queensland, Australia.

Abstract

Importance:

This analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti-programmed cell death 1 receptor inhibitors.

Objective:

To compare the 3-year survival with nivolumab vs that with dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma.

Design, Setting, and Participants:

This follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-blind CheckMate 066 phase 3 clinical trial. For this ongoing, multicenter academic institution trial, patients were enrolled from January 2013 through February 2014. Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without a BRAF mutation.

Interventions:

Patients were treated until progression or unacceptable toxic events with nivolumab (3 mg/kg every 2 weeks plus dacarbazine-matched placebo every 3 weeks) or dacarbazine (1000 mg/m2 every 3 weeks plus nivolumab-matched placebo every 2 weeks).

Main Outcome and Measure:

Overall survival.

Results:

At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group (median age, 64 years [range, 18-86 years]; 57.6% male) and 38.5 months among 208 participants in the dacarbazine group (median age, 66 years [range, 25-87 years]; 60.1% male), 3-year overall survival rates were 51.2% (95% CI, 44.1%-57.9%) and 21.6% (95% CI, 16.1%-27.6%), respectively. The median overall survival was 37.5 months (95% CI, 25.5 months-not reached) in the nivolumab group and 11.2 months (95% CI, 9.6-13.0 months) in the dacarbazine group (hazard ratio, 0.46; 95% CI, 0.36-0.59; P < .001). Complete and partial responses, respectively, were reported for 19.0% (40 of 210) and 23.8% (50 of 210) of patients in the nivolumab group compared with 1.4% (3 of 208) and 13.0% (27 of 208) of patients in the dacarbazine group. Additional analyses were performed on outcomes with subsequent therapies. Treatment-related grade 3/4 adverse events occurred in 15.0% (31 of 206) of nivolumab-treated patients and in 17.6% (36 of 205) of dacarbazine-treated patients. There were no deaths due to study drug toxic effects.

Conclusions and Relevance:

Nivolumab led to improved 3-year overall survival vs dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma.

Trial Registration:

ClinicalTrials.gov identifier: NCT01721772.

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