E M Hersh1, M Del Vecchio2, M P Brown3, R Kefford4, C Loquai5, A Testori6, S Bhatia7, R Gutzmer8, R Conry9, A Haydon10, C Robert11, S Ernst12, J Homsi13, J J Grob14, K Kendra15, S S Agarwala16, M Li17, A Clawson17, C Brachmann17, M Karnoub17, I Elias17, M F Renschler17, A Hauschild18. 1. Department of Medicine, Arizona Cancer Center, Tucson, USA ehersh@azcc.arizona.edu. 2. Department of Medical Oncology, Fondazione IRCCS National Tumor Institute, Milan, Italy. 3. Cancer Clinical Trials Unit, Royal Adelaide Hospital and School of Medicine, University of Adelaide, Adelaide. 4. Sydney West Cancer Trials Centre/Westmead Hospital and Melanoma Institute Australia, University of Sydney, North Sydney, Australia. 5. Department of Dermatology, University of Mainz, Mainz, Germany. 6. Melanoma and Muscle Cutaneous Sarcoma Division, European Institute of Oncology, Milan, Italy. 7. Department of Medicine, Seattle Cancer Care Alliance, Seattle, USA. 8. Department of Dermatology and Oncology, Hannover Medical School, Hannover, Germany. 9. Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, USA. 10. Department of Medical Oncology, Alfred Hospital, Melbourne, Australia. 11. Demartology Unit, Department of Medicine, The Gustave Roussy Cancer Institute, Villejuif, France. 12. Department of Medical Oncology, London Health Sciences Center-London Regional Cancer Program, London, Canada. 13. Department of Medical Oncology, Banner MD Anderson Cancer Center, Gilbert, USA. 14. Department of Dermatology, Timone Hospital, APHM and Aix-Marseille University, Marseille, France. 15. Department of Internal Medicine, Division of Medical Oncology, Ohio State University Comprehensive Cancer Center, Columbus. 16. Department of Hematology and Oncology, St Luke's Cancer Center and Temple University, Bethlehem. 17. Biometrics and Data Operations/Translational Medicine/Biometrics and Data Operations/Clinical Research & Development/Global Medical Affairs, Celgene Corporation, Summit, USA. 18. Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany.
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. PATIENTS AND 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.
RCT Entities:
BACKGROUND: The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. PATIENTS AND 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.
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