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

In Hae Park, Joo Hyuk Sohn, Sung Bae Kim, Keun Seok Lee, Joo Seop Chung, Soo Hyeon Lee, Tae You Kim, Kyung Hae Jung, Eun Kyung Cho, Yang Soo Kim, Hong Suk Song, Jae Hong Seo, Hun Mo Ryoo, Sun Ah Lee, So Young Yoon, Chul Soo Kim, Yong Tai Kim, Si Young Kim, Mi Ryung Jin, Jungsil Ro

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose 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). Materials and Methods Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 intravenously 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. Conclusion 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.

Original languageEnglish
Pages (from-to)569-577
Number of pages9
JournalCancer Research and Treatment
Volume49
Issue number3
DOIs
Publication statusPublished - 2017 Jul 1

Fingerprint

Micelles
Paclitaxel
Breast Neoplasms
Safety
Confidence Intervals
Peripheral Nervous System Diseases
Neutropenia
Disease-Free Survival
Molecular Weight
Survival
Incidence
cremophor EL
Therapeutics

Keywords

  • Cremophor EL-free
  • Genexol-PM
  • Metastatic breast cancer
  • Polymeric micelle paclitaxel

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / 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.

In: Cancer Research and Treatment, Vol. 49, No. 3, 01.07.2017, p. 569-577.

Research output: Contribution to journalArticle

Park, IH, Sohn, JH, Kim, SB, Lee, KS, Chung, JS, Lee, SH, Kim, TY, Jung, KH, Cho, EK, Kim, YS, Song, HS, Seo, JH, Ryoo, HM, Lee, SA, Yoon, SY, Kim, CS, Kim, YT, Kim, SY, Jin, MR & Ro, J 2017, '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', Cancer Research and Treatment, vol. 49, no. 3, pp. 569-577. https://doi.org/10.4143/crt.2016.289
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. / 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. In: Cancer Research and Treatment. 2017 ; Vol. 49, No. 3. pp. 569-577.
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abstract = "Purpose 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). Materials and Methods Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 intravenously 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. Conclusion 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.",
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TY - JOUR

T1 - 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

AU - Park, In Hae

AU - Sohn, Joo Hyuk

AU - Kim, Sung Bae

AU - Lee, Keun Seok

AU - Chung, Joo Seop

AU - Lee, Soo Hyeon

AU - Kim, Tae You

AU - Jung, Kyung Hae

AU - Cho, Eun Kyung

AU - Kim, Yang Soo

AU - Song, Hong Suk

AU - Seo, Jae Hong

AU - Ryoo, Hun Mo

AU - Lee, Sun Ah

AU - Yoon, So Young

AU - Kim, Chul Soo

AU - Kim, Yong Tai

AU - Kim, Si Young

AU - Jin, Mi Ryung

AU - Ro, Jungsil

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Purpose 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). Materials and Methods Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 intravenously 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. Conclusion 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.

AB - Purpose 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). Materials and Methods Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 intravenously 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. Conclusion 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.

KW - Cremophor EL-free

KW - Genexol-PM

KW - Metastatic breast cancer

KW - Polymeric micelle paclitaxel

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U2 - 10.4143/crt.2016.289

DO - 10.4143/crt.2016.289

M3 - Article

VL - 49

SP - 569

EP - 577

JO - Cancer Research and Treatment

JF - Cancer Research and Treatment

SN - 1598-2998

IS - 3

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