Final overall survival results of a randomized trial comparing bortezomib plus pegylated liposomal doxorubicin with bortezomib alone in patients with relapsed or refractory multiple myeloma.
Final overall survival results of a randomized trial comparing bortezomib plus pegylated liposomal doxorubicin with bortezomib alone in patients with relapsed or refractory multiple myeloma.
复制标题
DOI：
10.1002/cncr.30026
复制
发表时间：
2016-07-01
期刊：
影响因子：
6.2
通讯作者：
San-Miguel JF
中科院分区：
文献类型：
--
作者：
Orlowski RZ;Nagler A;Sonneveld P;Bladé J;Hajek R;Spencer A;Robak T;Dmoszynska A;Horvath N;Spicka I;Sutherland HJ;Suvorov AN;Xiu L;Cakana A;Parekh T;San-Miguel JF
先前一项开放标签、随机、3期研究的中期分析结果表明，硼替佐米联合聚乙二醇化脂质体多柔比星（PLD）治疗复发/难治性多发性骨髓瘤患者优于硼替佐米单药治疗，这些患者先前接受过一种或多种治疗。这里提供了该研究方案定义的最终生存数据。患者随机（1:1）接受单独硼替佐米（1.3 mg/m2，每21天周期的第1、4、8和11天静脉注射）或硼替佐米-PLD（硼替佐米加PLD 30mg /m2，第4天静脉注射）。主要终点是进展时间。次要疗效终点包括总生存期（OS）、无进展生存期和总有效率。2004年12月至2006年3月，共有646例患者（硼替佐米- pld， n = 324；硼替佐米单用，n = 322）被随机分组。在最终生存分析的临床截止日期（2014年5月16日），中位随访103个月时，79%的患者死亡（硼替佐米- pld组：324例患者中253例；78%；硼替佐米单独组：322例患者中257例；80%）。硼替佐米- pld组的中位生存期为33个月（95%可信区间[CI]， 28.9-37.1），而单独硼替佐米组的中位生存期为30.8个月（95% CI, 25.2-36.5）（风险比，1.047;95% CI, 0.879-1.246; P = 0.6068）。救助疗法包括传统药物和新型药物，两种治疗组之间平衡良好。尽管诱导了更长的进展时间，但长期随访显示，与单独使用硼替佐米相比，pld -硼替佐米并没有改善复发/难治性多发性骨髓瘤患者的OS。无法维持早期观察到的生存优势可能是由后续治疗线的影响引起的，这强调了需要对3期试验进行长期随访，同时认识到有足够的能力来检测长期OS差异的挑战。
Previous results from an interim analysis of an open-label, randomized, phase 3 study demonstrated that bortezomib combined with pegylated liposomal doxorubicin (PLD) was superior to bortezomib monotherapy in patients with relapsed/refractory multiple myeloma who had previously received one or more lines of therapy. Protocol-defined final survival data from that study are provided here. Patients were randomized (1:1) to receive either bortezomib alone (1.3 mg/m2 intravenously on days 1, 4, 8, and 11 of every 21-day cycle) or bortezomib-PLD (bortezomib plus PLD 30 mg/m2 intravenously on day 4). The primary endpoint was the time to progression. Secondary efficacy endpoints included overall survival (OS), progression-free survival, and the overall response rate. In total, 646 patients (bortezomib-PLD, n = 324; bortezomib alone, n = 322) were randomized between December, 2004, and March, 2006. On the clinical cutoff date (May 16, 2014) for the final survival analysis, at a median follow-up of 103 months, 79% of patients had died (bortezomib-PLD group: 253 of 324 patients; 78%; bortezomib alone group: 257 of 322 patients; 80%). The median OS in the bortezomib-PLD group was 33 months (95% confidence interval [CI], 28.9–37.1) versus 30.8 months (95% CI, 25.2–36.5) in the bortezomib alone group (hazard ratio, 1.047; 95% CI, 0.879–1.246; P = .6068). Salvage therapies included conventional and novel drugs, which were well balanced between the two treatment groups. Despite inducing a superior time to progression, long-term follow-up revealed that PLD-bortezomib did not improve OS compared with bortezomib alone in patients with relapsed/refractory multiple myeloma. The inability to sustain the early observed survival advantage may have been caused by the effects of subsequent lines of therapy, and underscores the need for long-term follow-up of phase 3 trials while recognizing the challenge of having adequate power to detect long-term differences in OS.
登录
查看更多内容
影响因子：
45.3
作者：
Jakubowiak, Andrzej J.;Kendall, Tara;Kaminski, Mark S.
通讯作者：
Kaminski, Mark S.
影响因子：
20.3
作者：
Offidani, Massimo;Corvatta, Laura;Leoni, Pietro
通讯作者：
Leoni, Pietro
影响因子：
6.2
作者：
Sonneveld, Pieter;Hajek, Roman;Orlowski, Robert Z.
通讯作者：
Orlowski, Robert Z.
影响因子：
20.3
作者：
Mitsiades, N;Mitsiades, CS;Anderson, KC
通讯作者：
Anderson, KC
影响因子：
45.3
作者：
Orlowski, Robert Z.;Nagler, Arnon;Harousseau, Jean-Luc
通讯作者：
Harousseau, Jean-Luc