title: A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma.
abstract: BACKGROUND
  The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial.
  
  
  METHODS
  Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m(2) on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m(2) every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS).
  
  
  RESULTS
  A total of 529 patients were randomized to nab-paclitaxel (n = 264) or dacarbazine (n = 265). Baseline characteristics were well balanced. The majority of patients were men (66%), had an Eastern Cooperative Oncology Group status of 0 (71%), and had M1c stage disease (65%). The median PFS (primary end point) was 4.8 months with nab-paclitaxel and 2.5 months with dacarbazine [hazard ratio (HR), 0.792; 95.1% confidence interval (CI) 0.631-0.992; P = 0.044]. The median OS was 12.6 months with nab-paclitaxel and 10.5 months with dacarbazine (HR, 0.897; 95.1% CI 0.738-1.089; P = 0.271). Independently assessed overall response rate was 15% versus 11% (P = 0.239), and disease control rate (DCR) was 39% versus 27% (P = 0.004) for nab-paclitaxel versus dacarbazine, respectively. The most common grade ≥3 treatment-related adverse events were neuropathy (nab-paclitaxel, 25% versus dacarbazine, 0%; P < 0.001), and neutropenia (nab-paclitaxel, 20% versus dacarbazine, 10%; P = 0.004). There was no correlation between secreted protein acidic and rich in cysteine (SPARC) status and PFS in either treatment arm.
  
  
  CONCLUSIONS
  nab-Paclitaxel significantly improved PFS and DCR compared with dacarbazine, with a manageable safety profile.
authors.affiliation: Department of Medicine, Arizona Cancer Center, Tucson, USA ehersh@azcc.arizona.edu.
authors.forename: E M
authors.initials: EM
authors.lastname: Hersh
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS National Tumor Institute, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Del Vecchio
authors.affiliation: Cancer Clinical Trials Unit, Royal Adelaide Hospital and School of Medicine, University of Adelaide, Adelaide.
authors.forename: M P
authors.initials: MP
authors.lastname: Brown
authors.affiliation: Sydney West Cancer Trials Centre/Westmead Hospital and Melanoma Institute Australia, University of Sydney, North Sydney, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Kefford
authors.affiliation: Department of Dermatology, University of Mainz, Mainz, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Loquai
authors.affiliation: Melanoma and Muscle Cutaneous Sarcoma Division, European Institute of Oncology, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Testori
authors.affiliation: Department of Medicine, Seattle Cancer Care Alliance, Seattle, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: Department of Dermatology and Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Gutzmer
authors.affiliation: Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, USA.
authors.forename: R
authors.initials: R
authors.lastname: Conry
authors.affiliation: Department of Medical Oncology, Alfred Hospital, Melbourne, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Haydon
authors.affiliation: Demartology Unit, Department of Medicine, The Gustave Roussy Cancer Institute, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Robert
authors.affiliation: Department of Medical Oncology, London Health Sciences Center-London Regional Cancer Program, London, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Ernst
authors.affiliation: Department of Medical Oncology, Banner MD Anderson Cancer Center, Gilbert, USA.
authors.forename: J
authors.initials: J
authors.lastname: Homsi
authors.affiliation: Department of Dermatology, Timone Hospital, APHM and Aix-Marseille University, Marseille, France.
authors.forename: J J
authors.initials: JJ
authors.lastname: Grob
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Ohio State University Comprehensive Cancer Center, Columbus.
authors.forename: K
authors.initials: K
authors.lastname: Kendra
authors.affiliation: Department of Hematology and Oncology, St Luke's Cancer Center and Temple University, Bethlehem.
authors.forename: S S
authors.initials: SS
authors.lastname: Agarwala
authors.affiliation: Biometrics and Data Operations/Translational Medicine/Biometrics and Data Operations/Clinical Research & Development/Global Medical Affairs, Celgene Corporation, Summit, USA.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Biometrics and Data Operations/Translational Medicine/Biometrics and Data Operations/Clinical Research & Development/Global Medical Affairs, Celgene Corporation, Summit, USA.
authors.forename: A
authors.initials: A
authors.lastname: Clawson
authors.affiliation: Biometrics and Data Operations/Translational Medicine/Biometrics and Data Operations/Clinical Research & Development/Global Medical Affairs, Celgene Corporation, Summit, USA.
authors.forename: C
authors.initials: C
authors.lastname: Brachmann
authors.affiliation: Biometrics and Data Operations/Translational Medicine/Biometrics and Data Operations/Clinical Research & Development/Global Medical Affairs, Celgene Corporation, Summit, USA.
authors.forename: M
authors.initials: M
authors.lastname: Karnoub
authors.affiliation: Biometrics and Data Operations/Translational Medicine/Biometrics and Data Operations/Clinical Research & Development/Global Medical Affairs, Celgene Corporation, Summit, USA.
authors.forename: I
authors.initials: I
authors.lastname: Elias
authors.affiliation: Biometrics and Data Operations/Translational Medicine/Biometrics and Data Operations/Clinical Research & Development/Global Medical Affairs, Celgene Corporation, Summit, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Renschler
authors.affiliation: Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hauschild
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D003606:Dacarbazine / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000188:drug therapy*; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D017239:Paclitaxel
keywords: BRAF; chemotherapy-naïve; dacarbazine; metastatic melanoma; nab-Paclitaxel