Randomized phase III trial of gemcitabine plus docetaxel plus bevacizumab or placebo as first-line treatment for metastatic uterine leiomyosarcoma: An NRG oncology/ Gynecologic Oncology Group study Journal Article


Authors: Hensley, M. L.; Miller, A.; O'Malley, D. M.; Mannel, R. S.; Behbakht, K.; Bakkum-Gamez, J. N.; Michael, H.
Article Title: Randomized phase III trial of gemcitabine plus docetaxel plus bevacizumab or placebo as first-line treatment for metastatic uterine leiomyosarcoma: An NRG oncology/ Gynecologic Oncology Group study
Abstract: Purpose Fixed-dose rate gemcitabine plus docetaxel achieves objective response in 35% of patients with uterine leiomyosarcoma (uLMS). This study aimed to determine whether the addition of bevacizumab to gemcitabine-docetaxel increases progression-free survival (PFS) in uLMS. Patients and Methods In this phase III, double-blind, placebo-controlled trial, patients with chemotherapy-naive, metastatic, unresectable uLMS were randomly assigned to gemcitabine-docetaxel plus bevacizumab or gemcitabine-docetaxel plus placebo. PFS, overall survival (OS), and objective response rates (ORRs) were compared to determine superiority. Target accrual was 130 patients to detect an increase in median PFS from 4 months (gemcitabine-docetaxel plus placebo) to 6.7 months (gemcitabine-docetaxel plus bevacizumab). Treatment effects on PFS and OS were described by hazard ratios (HRs), median times to event, and 95% CIs. Results In all, 107 patients were accrued: gemcitabine-docetaxel plus placebo (n - 54) and gemcitabinedocetaxel plus bevacizumab (n - 53). Accrual was stopped early for futility. No statistically significant differences in grade 3 to 4 toxicities were observed. Median PFS was 6.2 months for gemcitabine-docetaxel plus placebo versus 4.2 months for gemcitabine-docetaxel plus bevacizumab (HR, 1.12; P - .58). Median OS was 26.9 months for gemcitabine-docetaxel plus placebo and 23.3 months for gemcitabine-docetaxel plus bevacizumab (HR, 1.07; P - .81). Objective responses were observed in 17 (31.5%) of 54 patients randomly assigned to gemcitabinedocetaxel plus placebo and 19 (35.8%) of 53 patients randomly assigned to gemcitabine-docetaxel plus bevacizumab. Mean duration of response was 8.6 months for gemcitabine-docetaxel plus placebo versus 8.8 months for gemcitabine-docetaxel plus bevacizumab. Conclusion The addition of bevacizumab to gemcitabine-docetaxel for first-line treatment of metastatic uLMS failed to improve PFS, OS, or ORR. Gemcitabine-docetaxel remains a standard first-line treatment for uLMS. © 2015 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 33
Issue: 10
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2015-04-01
Start Page: 1180
End Page: 1185
Language: English
DOI: 10.1200/jco.2014.58.3781
PROVIDER: scopus
PMCID: PMC4372854
PUBMED: 25713428
DOI/URL:
Notes: Export Date: 4 May 2015 -- Source: Scopus
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MSK Authors
  1. Martee L Hensley
    257 Hensley