Phase III trial of carboplatin and paclitaxel with or without sorafenib in metastatic melanoma.

Abstract

PURPOSE:

The primary objective of this study was to determine whether carboplatin, paclitaxel, and sorafenib (CPS) improve overall survival (OS) compared with carboplatin and paclitaxel (CP) in chemotherapy-naive patients with metastatic melanoma.

PATIENTS AND METHODS:

In this double-blind, randomized, placebo-controlled phase III study, all patients received carboplatin at area under the [concentration-time] curve 6 and paclitaxel 225 mg/m(2) intravenously once every 21 days with random assignment to sorafenib 400 mg orally twice per day on days 2 through 19 every 21 days or placebo. The primary end point was OS, and secondary end points included progression-free survival, objective tumor response, and toxicity.

RESULTS:

In all, 823 patients were enrolled over 34 months. At final analysis, the median OS was 11.3 months (95% CI, 9.8 to 12.2 months) for CP and 11.1 months (95% CI, 10.3 to 12.3 months) for CPS; the difference in the OS distribution was not statistically significant by the stratified log-rank test, stratified on American Joint Committee on Cancer (AJCC) stage, Eastern Cooperative Oncology Group (ECOG) performance status, and prior therapy (P = .878). Median progression-free survival was 4.9 months for CPS and 4.2 months for CP (P = .092, stratified log-rank test). Response rate was 20% for CPS and 18% for CP (P = .427). More patients on the CPS arm had grade 3 or higher toxicities (84% v 78%; P = .027), with increased rash, hand-foot syndrome, and thrombocytopenia accounting for most of the difference.

CONCLUSION:

Sorafenib does not improve OS when given in combination with CP for chemotherapy-naive patients with metastatic melanoma. This study establishes benchmark end points for the CP regimen in first-line therapy of metastatic melanoma.

• Authors: Keith T Flaherty, Sandra J Lee, Fengmin Zhao, Lynn M Schuchter, Lawrence Flaherty, Richard Kefford, Michael B Atkins, Philip Leming, John M Kirkwood
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 31 Issue 3 Pg. 373-9 (Jan 20 2013) ISSN: 1527-7755 [Electronic] United States
• PMID: 23248256 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Phenylurea Compounds
• Niacinamide
• Sorafenib
• Carboplatin
• Paclitaxel

Topics

• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Carboplatin (administration & dosage, adverse effects)
• Disease-Free Survival
• Double-Blind Method
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Melanoma (drug therapy, mortality)
• Middle Aged
• Niacinamide (administration & dosage, adverse effects, analogs & derivatives)
• Paclitaxel (administration & dosage, adverse effects)
• Phenylurea Compounds (administration & dosage, adverse effects)
• Sorafenib