Global phase III study of gemcitabine plus paclitaxel (GT) vs. paclitaxel (T) as frontline therapy for metastatic breast cancer (MBC): First report of overall surviva.
Global phase III study of gemcitabine plus paclitaxel (GT) vs. paclitaxel (T) as frontline therapy for metastatic breast cancer (MBC): First report of overall surviva.
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吉西他滨联合紫杉醇 (GT) 与紫杉醇 (T) 作为转移性乳腺癌 (MBC) 一线治疗的全球 III 期研究：总体生存率的第一份报告。
DOI：
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发表时间：
2004
影响因子：
45.3
通讯作者：
J. Reyes
中科院分区：
文献类型：
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作者：
K S Albain;S. Nag;G. Calderillo;Johann Petrus Jordaan;A. Llombart;Anna Pluzanska;M. Pawlicki;A. Melemed;J. O'Shaughnessy;J. Reyes
510 背景：GT 在接受蒽环类药物治疗 MBC 后具有 II 期安全性和有效性，因此在一线治疗的 III 期研究中将其与 T 进行了比较。应计目标于 4 月 2 日实现，在最初计划的中期分析中，GT 显着改善了进展时间 (TTP)、无进展生存期 (PFS)、客观缓解率 (ORR) 和生活质量，并具有可接受的毒性特征 (PASCO 22:161, 2003)。目前还不确定这是否会转化为试验的主要终点——总生存期（OS）获益。本报告提出了第一份操作系统分析。
方法
具有可测量的 MBC、既往接受（新）辅助蒽环类药物且 KPS ≥70 的患者（患者）在进展前第 21 天随机接受 GT（G 1250 mg/m2 d1,8；T 175 mg/m2 d1）或 T（175 mg/m2 d1）组。中位随访时间为 15.6 个月（除 1 点外均偏离研究），通过 Kaplan-Meier 和 Cox 回归进行的第一次 OS 分析是在计划最终 OS 报告所需死亡人数 (440) 的大约 75% (343) 时进行的。 （所有 p 值都是双侧的；置信区间为 95%。） 结果：529 名患有内脏为主疾病的合格患者（267 GT，262 T）的特征；毒性; GT 在 ORR、TTP 和 PFS 方面的显着益处之前已有报道（参见上文）。 GT 组中 38% 的患者因病情进展而停止治疗，而 T 组中这一比例为 55%；治疗因不良事件而结束，GT 为 6.7%，T 为 5.0%。OS 风险比 (HR) 为 0.775 (.627, .959)，支持 GT，p=.018。 GT 的中位 OS 为 18.5 mos (16.5-21.2)，而 T 为 15.8 mos (14.4-17.4)。 GT 的一年生存率为 70.7% (65.1-76.3%)，T 的一年生存率为 60.9% (54.8-66.9%) (p=.019)。调整基线协变量后，支持 GT 的 HR 在 Cox 回归中持续存在：0.740 (.598, .915)，p=.006。除了 T 臂中吉西他滨的使用量增加了 4 倍之外，各臂之间的二线治疗几乎相同。
结论
当两者均以第 3 周为周期进行治疗时，GT 比 T 具有显着的 OS 优势，这一结果将在 2004 年底的最终计划分析中得到证实。TTP 的益处预测 OS 会随着更长的随访时间而改善。 GT 应被视为 MBC 的一线治疗方案。 [表：见正文]。
510 Background: GT had phase II safety and efficacy in MBC after anthracyclines, so it was compared to T in a phase III study of frontline therapy. Accrual goals were met in 4/02 and at initial planned interim analysis, GT significantly improved time to progression (TTP), progression-free survival (PFS), objective response rates (ORR) and quality of life, with an acceptable toxicity profile (PASCO 22:161, 2003). It was uncertain if this would translate into overall survival (OS) benefit, the primary endpoint of the trial. This report presents the first OS analysis.
METHODS
Patients (pts) with measurable MBC, prior (neo)adjuvant anthracyclines and KPS ≥70 were randomized to GT (G 1250 mg/m2 d1,8; T 175 mg/m2 d1) or T (175 mg/m2 d1) q21 days to progression. With median follow-up of 15.6 mos (all but 1 pt off study), the first OS analyses by Kaplan-Meier and Cox regression were conducted at approximately 75% (343) of the deaths needed (440) for the planned final OS report. (All p-values are 2-sided; confidence intervals, 95%.) Results: Characteristics of the 529 eligible pts (267 GT, 262 T) with visceral-dominant disease; toxicity; and the significant benefit from GT in ORR, TTP and PFS were previously reported (ref. above). 38% on GT stopped therapy due to progression vs 55% on T; therapy ended due to adverse events in 6.7%, GT vs 5.0%, T. The OS hazard ratio (HR) was 0.775 (.627, .959) in favor of GT, p=.018. Median OS for GT was 18.5 mos (16.5-21.2) vs T, 15.8 mos (14.4-17.4). One-year survival was 70.7% (65.1-76.3%) for GT and 60.9% (54.8-66.9%) for T (p=.019). The HR in favor of GT persisted in Cox regression after adjusting for baseline covariates: 0.740 (.598, .915), p=.006. Second-line therapy was nearly identical between arms, except for a 4-fold greater use of gemcitabine in the T arm.
CONCLUSIONS
GT provides significant OS advantage over T when both are given on a q3 week cycle, a result to be confirmed in the final planned analysis in late 2004. The TTP benefit predicted OS improvement with longer follow-up. GT should be considered a frontline regimen in MBC. [Table: see text].