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.
Author(s): Hensley ML(1), Miller A(2), O'Malley DM(2), Mannel RS(2), Behbakht K(2),
Bakkum-Gamez JN(2), Michael H(2).
Affiliation(s): Author information:
(1)Martee L. Hensley, Memorial Sloan-Kettering Cancer Center and Weill Cornell
Medical College, New York; Austin Miller, NRG Oncology, Buffalo, NY; David M.
O'Malley, The Ohio State University, Columbus, OH; Robert S. Mannel, University
of Oklahoma, Oklahoma City, OK; Kian Behbakht, University of Colorado Denver,
Aurora, CO; Jamie N. Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael,
Indiana University School of Medicine, Indianapolis, IN. gynbreast@mskcc.org.
(2)Martee L. Hensley, Memorial Sloan-Kettering Cancer Center and Weill Cornell
Medical College, New York; Austin Miller, NRG Oncology, Buffalo, NY; David M.
O'Malley, The Ohio State University, Columbus, OH; Robert S. Mannel, University
of Oklahoma, Oklahoma City, OK; Kian Behbakht, University of Colorado Denver,
Aurora, CO; Jamie N. Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael,
Indiana University School of Medicine, Indianapolis, IN.
Publication date & source: 2015, J Clin Oncol. , 33(10):1180-5
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 gemcitabine-docetaxel 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 gemcitabine-docetaxel 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.
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