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.
OBJECTIVE
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).


METHODS
Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2or Genexol 175 mg/m2intravenously every 3 weeks. The primary outcome was the objective response rate (ORR).


RESULTS
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/m2(95.0%), and that of Genexol was 168.3±10.6 mg/m2(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) (pnon-inferiority=0.021, psuperiority=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.


CONCLUSIONS
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.
Center for Breast Cancer, National Cancer Center, Goyang, Korea.
In Hae
IH
Park
Department of Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Joo Hyuk
JH
Sohn
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Sung Bae
SB
Kim
Center for Breast Cancer, National Cancer Center, Goyang, Korea.
Keun Seok
KS
Lee
Division of Hematology-Oncology, Pusan National University Hospital, Busan, Korea.
Joo Seop
JS
Chung
Department of Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Soo Hyeon
SH
Lee
Medical Oncology Center, Seoul National University Hospital, Seoul, Korea.
Tae You
TY
Kim
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Kyung Hae
KH
Jung
Division of Hematology-Oncology, Gachon University Gil Medical Center, Incheon, Korea.
Eun Kyung
EK
Cho
Division of Hematology-Oncology, Kosin University Gospel Hospital, Busan, Korea.
Yang Soo
YS
Kim
Division of HematologyOncology, Keimyung University Dongsan Medical Center, Daegu, Korea.
Hong Suk
HS
Song
Department of Hematology-Oncology, Korea University Guro Hospital, Seoul, Korea.
Jae Hong
JH
Seo
Division of HematologyOncology, Daegu Catholic University Medical Center, Daegu, Korea.
Hun Mo
HM
Ryoo
Division of Hematology-Oncology, Daegu Fatima Hospital, Daegu, Korea.
Sun Ah
SA
Lee
Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
So Young
SY
Yoon
Division of Hematology-Oncology, Inha University Hospital, Incheon, Korea.
Chul Soo
CS
Kim
Division of Hematology-Oncology, National Health Insurance Service Ilsan Hospital, Goyang, Korea.
Yong Tai
YT
Kim
Division of Hematology-Oncology, Kyung Hee University Medical Center, Seoul, Korea.
Si Young
SY
Kim
Samyang Biopharmaceuticals Corporation, Seoul, Korea.
Mi Ryung
MR
Jin
Center for Breast Cancer, National Cancer Center, Goyang, Korea.
Jungsil
J
Ro
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D005990:Glycerol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008823:Micelles; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D011108:Polymers; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases; D012008:Recurrence; D019233:Retreatment; D012307:Risk Factors; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D005990:Glycerol; D008823:Micelles; D017239:Paclitaxel; D011108:Polymers; D018719:Erb-b2 Receptor Tyrosine Kinases; C000515:cremophor EL
Cremophor EL-free; Genexol-PM; Metastatic breast cancer; Polymeric micelle paclitaxel