Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study.
Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study.
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DOI：
10.1016/s1470-2045(13)70130-x
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Baselga J
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作者：
Swain SM;Kim SB;Cortés J;Ro J;Semiglazov V;Campone M;Ciruelos E;Ferrero JM;Schneeweiss A;Knott A;Clark E;Ross G;Benyunes MC;Baselga J
随机、双盲 3 期研究 CLEOPATRA 的初步结果表明，与安慰剂加曲妥珠单抗加多西他赛相比，帕妥珠单抗加曲妥珠单抗加多西他赛可显着改善人表皮生长因子受体 2 (HER2) 阳性一线转移性乳腺癌 (MBC) 患者的中位无进展生存期 (PFS)。初步分析的总生存 (OS) 数据显示出有利于帕妥珠单抗组的强烈趋势，但未达到统计学显着性。在此，我们报告了经过一年的随访后确认的 OS 结果。患者被随机分配接受研究治疗。使用 Kaplan-Meier 方法和按地理区域和既往治疗状态分层的对数秩检验对 OS 和研究者评估的 PFS 进行分析。该试验已在 ClinicalTrials.gov 注册，NCT00567190。在意向治疗人群（808 名患者）中，截至数据截止时已发生 267 例死亡（安慰剂组：406 例中的 154 例 [37·9%]，帕妥珠单抗组：402 例中的 113 例 [28·1%]）。帕妥珠单抗加曲妥珠单抗加多西他赛治疗导致研究过程中死亡风险降低 34%（HR=0·66；95% CI 0·52–0·84；p=0·0008）。安慰剂组的中位 OS 为 37·6 个月，而帕妥珠单抗组尚未达到。对研究者评估的 PFS 进行描述性随访分析显示，安慰剂组与帕妥珠单抗组的中位 PFS 分别为 12·4 和 18·7 个月（HR=0·69；95% CI 0·58–0·81）。经过一年的跟踪，没有发现新的安全问题。不良事件在发生率、严重程度和特异性方面与初步分析中报告的不良事件相似。该 OS 分析表明，帕妥珠单抗加曲妥珠单抗加多西他赛对 HER2 阳性 MBC 患者具有统计学意义和临床意义的生存获益。研究者评估的 PFS 和安全性的更新分析与初步分析的结果一致。 F.霍夫曼-拉罗氏/基因泰克
Primary results from the randomised, double-blind phase 3 study CLEOPATRA demonstrated significantly improved median progression-free survival (PFS) with pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive first-line metastatic breast cancer (MBC). Overall survival (OS) data at the primary analysis showed a strong trend in favour of the pertuzumab arm but did not reach statistical significance. Here we report confirmatory OS results after one additional year of follow-up. Patients were randomly assigned to study treatment. OS and investigator-assessed PFS were analysed using the Kaplan-Meier approach and log-rank tests stratified by geographic region and prior treatment status. This trial is registered with ClinicalTrials.gov, NCT00567190. In the intent-to-treat population (808 patients), 267 deaths had occurred at data cut-off (placebo arm: 154 of 406 [37·9%], pertuzumab arm: 113 of 402 [28·1%]). Treatment with pertuzumab plus trastuzumab plus docetaxel resulted in a 34% reduction in the risk of death during the course of the study (HR=0·66; 95% CI 0·52–0·84; p=0·0008). Median OS was 37·6 months in the placebo arm and was not yet reached in the pertuzumab arm. A descriptive follow-up analysis of investigator-assessed PFS showed a median PFS of 12·4 and 18·7 months in the placebo versus pertuzumab arm (HR=0·69; 95% CI 0·58–0·81). No new safety concerns were identified with one additional year of follow-up. Adverse events were similar to those reported at the primary analysis with respect to incidence, severity, and specificity. This OS analysis demonstrated statistically significant and clinically meaningful survival benefit with pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive MBC. Updated analyses of investigator-assessed PFS and safety were consistent with the results from the primary analysis. F. Hoffmann-La Roche/Genentech