Hensley Martee L, Miller Austin, O'Malley David M, Mannel Robert S, Behbakht Kian, Bakkum-Gamez Jamie N, Michael Helen
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.
J Clin Oncol. 2015 Apr 1;33(10):1180-5. doi: 10.1200/JCO.2014.58.3781. Epub 2015 Feb 23.
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.
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.
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.
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.
固定剂量率的吉西他滨联合多西他赛可使35%的子宫平滑肌肉瘤（uLMS）患者获得客观缓解。本研究旨在确定在吉西他滨 - 多西他赛方案中加入贝伐单抗是否能提高uLMS患者的无进展生存期（PFS）。
在这项III期、双盲、安慰剂对照试验中，未接受过化疗、转移性、不可切除的uLMS患者被随机分配至吉西他滨 - 多西他赛联合贝伐单抗组或吉西他滨 - 多西他赛联合安慰剂组。比较PFS、总生存期（OS）和客观缓解率（ORR）以确定优势。目标入组130例患者，以检测中位PFS从4个月（吉西他滨 - 多西他赛联合安慰剂）增加到6.7个月（吉西他滨 - 多西他赛联合贝伐单抗）。用风险比（HRs）、事件中位时间和95%置信区间描述对PFS和OS的治疗效果。
总共入组了107例患者：吉西他滨 - 多西他赛联合安慰剂组（n = 54）和吉西他滨 - 多西他赛联合贝伐单抗组（n = 53）。因无效性提前终止入组。未观察到3至4级毒性的统计学显著差异。吉西他滨 - 多西他赛联合安慰剂组的中位PFS为6.2个月，而吉西他滨 - 多西他赛联合贝伐单抗组为4.2个月（HR，1.12；P = 0.58）。吉西他滨 - 多西他赛联合安慰剂组的中位OS为26.9个月，吉西他滨 - 多西他赛联合贝伐单抗组为23.3个月（HR，1.07；P = 0.81）。在随机分配至吉西他滨 - 多西他赛联合安慰剂组的54例患者中，17例（31.5%）观察到客观缓解，在随机分配至吉西他滨 - 多西他赛联合贝伐单抗组的53例患者中，19例（35.8%）观察到客观缓解。吉西他滨 - 多西他赛联合安慰剂组的平均缓解持续时间为8.6个月，吉西他滨 - 多西他赛联合贝伐单抗组为8.8个月。
在转移性uLMS的一线治疗中，在吉西他滨 - 多西他赛方案中加入贝伐单抗未能改善PFS、OS或ORR。吉西他滨 - 多西他赛仍然是uLMS的标准一线治疗方案。
