A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma

Evan M. Hersh, M. Del Vecchio, M. P. Brown, R. Kefford, C. Loquai, A. Testori, S. Bhatia, R. Gutzmer, R. Conry, A. Haydon, C. Robert, S. Ernst, J. Homsi, J. J. Grob, K. Kendra, S. S. Agarwala, M. Li, A. Clawson, C. Brachmann, M. Karnoub & 3 others I. Elias, M. F. Renschler, A. Hauschild

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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/m2 on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m2 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.

Original languageEnglish
Article numbermdv324
Pages (from-to)2267-2274
Number of pages8
JournalAnnals of Oncology
Volume26
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

Fingerprint

Dacarbazine
Melanoma
Drug Therapy
Disease-Free Survival
Confidence Intervals
Safety
130-nm albumin-bound paclitaxel
Survival
Neutropenia
Cysteine
Randomized Controlled Trials

Keywords

  • BRAF
  • chemotherapy-naïve
  • dacarbazine
  • metastatic melanoma
  • nab-Paclitaxel

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma. / Hersh, Evan M.; Del Vecchio, M.; Brown, M. P.; Kefford, R.; Loquai, C.; Testori, A.; Bhatia, S.; Gutzmer, R.; Conry, R.; Haydon, A.; Robert, C.; Ernst, S.; Homsi, J.; Grob, J. J.; Kendra, K.; Agarwala, S. S.; Li, M.; Clawson, A.; Brachmann, C.; Karnoub, M.; Elias, I.; Renschler, M. F.; Hauschild, A.

In: Annals of Oncology, Vol. 26, No. 11, mdv324, 01.11.2015, p. 2267-2274.

Research output: Contribution to journalArticle

Hersh, EM, Del Vecchio, M, Brown, MP, Kefford, R, Loquai, C, Testori, A, Bhatia, S, Gutzmer, R, Conry, R, Haydon, A, Robert, C, Ernst, S, Homsi, J, Grob, JJ, Kendra, K, Agarwala, SS, Li, M, Clawson, A, Brachmann, C, Karnoub, M, Elias, I, Renschler, MF & Hauschild, A 2015, 'A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma', Annals of Oncology, vol. 26, no. 11, mdv324, pp. 2267-2274. https://doi.org/10.1093/annonc/mdv324
Hersh, Evan M. ; Del Vecchio, M. ; Brown, M. P. ; Kefford, R. ; Loquai, C. ; Testori, A. ; Bhatia, S. ; Gutzmer, R. ; Conry, R. ; Haydon, A. ; Robert, C. ; Ernst, S. ; Homsi, J. ; Grob, J. J. ; Kendra, K. ; Agarwala, S. S. ; Li, M. ; Clawson, A. ; Brachmann, C. ; Karnoub, M. ; Elias, I. ; Renschler, M. F. ; Hauschild, A. / A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma. In: Annals of Oncology. 2015 ; Vol. 26, No. 11. pp. 2267-2274.
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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-na{\"i}ve patients with stage IV melanoma received nab-paclitaxel 150 mg/m2 on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m2 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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T1 - A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma

AU - Hersh, Evan M.

AU - Del Vecchio, M.

AU - Brown, M. P.

AU - Kefford, R.

AU - Loquai, C.

AU - Testori, A.

AU - Bhatia, S.

AU - Gutzmer, R.

AU - Conry, R.

AU - Haydon, A.

AU - Robert, C.

AU - Ernst, S.

AU - Homsi, J.

AU - Grob, J. J.

AU - Kendra, K.

AU - Agarwala, S. S.

AU - Li, M.

AU - Clawson, A.

AU - Brachmann, C.

AU - Karnoub, M.

AU - Elias, I.

AU - Renschler, M. F.

AU - Hauschild, A.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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/m2 on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m2 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.

AB - 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/m2 on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m2 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.

KW - BRAF

KW - chemotherapy-naïve

KW - dacarbazine

KW - metastatic melanoma

KW - nab-Paclitaxel

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U2 - 10.1093/annonc/mdv324

DO - 10.1093/annonc/mdv324

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JO - Annals of Oncology

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