A randomized phase II study of weekly paclitaxel with or without pelareorep in patients with metastatic breast cancer: final analysis of Canadian Cancer Trials Group IND.213.
A randomized phase II study of weekly paclitaxel with or without pelareorep in patients with metastatic breast cancer: final analysis of Canadian Cancer Trials Group IND.213.
复制标题
DOI：
10.1007/s10549-017-4538-4
复制
发表时间：
2018-01-01
影响因子：
3.8
通讯作者：
Seymour, L.
中科院分区：
文献类型：
--
作者：
Bernstein, V.;Ellard, S. L.;Seymour, L.
Pelarorep 是一种血清型 3 呼肠孤病毒，已在乳腺癌中表现出临床前和早期临床活性，并与微管靶向药物具有协同细胞毒活性。这项多中心、随机、II 期试验旨在评估在紫杉醇中添加 pelareorep 对转移性乳腺癌 (mBC) 患者的疗效和安全性。在对 7 名患者进行安全磨合后，74 名既往接受过治疗的 mBC 女性被随机分配接受紫杉醇 80 mg/m(2) 静脉注射，每 4 周在第 1、8 和 15 天静脉注射紫杉醇 3 次每 4 周在第 1、2、8、9、15 和 16 天静脉注射 10(10) TCID50（A 组）或单独使用紫杉醇（B 组）。主要终点是无进展生存期（PFS）。次要终点是客观缓解率、总生存期（OS）、循环肿瘤细胞计数、安全性和探索性相关分析。所有比较均使用 20% alpha 水平的双边测试。生存分析针对之前的紫杉醇进行了调整。最终分析是在中位随访 29.5 个月后进行的。 Pelarorep 耐受性良好。 A 组患者具有更有利的基线预后变量。调整后的中位 PFS（A 组与 B 组）分别为 3.78 个月与 3.38 个月（HR 1.04，80% CI 0.76-1.43，P = 0.87）。两组之间的反应率没有差异（P = 0.87）。中位 OS（A 组与 B 组）分别为 17.4 个月与 10.4 个月（HR 0.65，80% CI 0.46-0.91，P = 0.1）。这项第一项 II 期随机研究在既往治疗的 mBC 中使用 pelareorep 和紫杉醇，未显示 PFS（主要终点）或 RR 存在差异。然而，该组合的操作系统明显更长。进一步探索转移性乳腺癌治疗方案可能值得关注。
Pelareorep, a serotype 3 reovirus, has demonstrated preclinical and early clinical activity in breast cancer and synergistic cytotoxic activity with microtubule targeting agents. This multicentre, randomized, phase II trial was undertaken to evaluate the efficacy and safety of adding pelareorep to paclitaxel for patients with metastatic breast cancer (mBC).Following a safety run-in of 7 patients, 74 women with previously treated mBC were randomized either to paclitaxel 80 mg/m(2) intravenously on days 1, 8, and 15 every 4 weeks plus pelareorep 3 x 10(10) TCID50 intravenously on days 1, 2, 8, 9, 15, and 16 every 4 weeks (Arm A) or to paclitaxel alone (Arm B). Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate, overall survival (OS), circulating tumour cell counts, safety, and exploratory correlative analyses. All comparisons used a two-sided test at an alpha level of 20%. Survival analyses were adjusted for prior paclitaxel.Final analysis was performed after a median follow-up of 29.5 months. Pelareorep was well tolerated. Patients in Arm A had more favourable baseline prognostic variables. Median adjusted PFS (Arm A vs B) was 3.78 mo vs 3.38 mo (HR 1.04, 80% CI 0.76-1.43, P = 0.87). There was no difference in response rate between arms (P = 0.87). Median OS (Arm A vs B) was 17.4 mo vs 10.4 mo (HR 0.65, 80% CI 0.46-0.91, P = 0.1).This first, phase II, randomized study of pelareorep and paclitaxel in previously treated mBC did not show a difference in PFS (the primary endpoint) or RR. However, there was a significantly longer OS for the combination. Further exploration of this regimen in mBC may be of interest.