An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer

• Published in: Cancer research and treatment 2017, 49(3), , pp.569-577
• Main Authors: Park, In Hae, Sohn, Joo Hyuk, Kim, Sung Bae, Lee, Keun Seok, Chung, Joo Seop, Lee, Soo Hyeon, Kim, Tae You, Jung, Kyung Hae, Cho, Eun Kyung, Kim, Yang Soo, Song, Hong Suk, Seo, Jae Hong, Ryoo, Hun Mo, Lee, Sun Ah, Yoon, So Young, Kim, Chul Soo, Kim, Yong Tai, Kim, Si Young, Jin, Mi Ryung, Ro, Jungsil
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Female; Glycerol - administration & dosage; Glycerol - adverse effects; Glycerol - analogs & derivatives; Humans; Micelles; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Original; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Polymers; Proportional Hazards Models; Receptor, ErbB-2; Recurrence; Retreatment; Risk Factors; Treatment Outcome; 의약학
• ISSN: 1598-2998; 2005-9256
• DOI: 10.4143/crt.2016.289

Genexol-PM is a Cremophor EL-free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m or Genexol 175 mg/m intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m (95.0%), and that of Genexol was 168.3±10.6 mg/m (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p =0.021, p =0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.