Introduction: We report detailed safety analyses by geographic region from the phase III study CLEOPATRA with pertuzumab, trastuzumab, and docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive first-line metastatic breast cancer.
Patients and methods: Patients received pertuzumab/placebo at 840 mg in cycle 1 and 420 mg in subsequent cycles, and trastuzumab at 8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles; docetaxel was initiated at 75 mg/m(2). All study drugs were given intravenously, 3 times weekly.
Results: Docetaxel dose reductions below 75 mg/m(2) were more common in patients from Asia (47.0%) than other regions (13.4%); docetaxel dose escalations to 100 mg/m(2) were less frequent in Asia (2.4%) than other regions (18.7%). Rates of edema (26.1% and 5.4% for Asia and other regions, respectively), myalgia (42.3%, 14.7%), nail disorder (39.9%, 15.1%), febrile neutropenia (18.6%, 7.1%), upper respiratory tract infection (25.7%, 10.2%), decreased appetite (47.0%, 19.1%), and rash (44.3%, 22.0%) were at least twice as high in Asia as in other regions. Adverse events did not result in a reduction in the median number of study treatment cycles administered in patients from Asia. Efficacy analyses per region showed hazard ratios similar to those of the whole intention-to-treat (ITT) population for progression-free survival (ITT: 0.63; Asia: 0.68; other regions: 0.61) and overall survival (ITT: 0.66; Asia: 0.64; other regions: 0.66).
Conclusion: Despite a higher proportion of docetaxel dose reductions in patients from Asia, survival benefits were comparable between regions. The benefit-risk profile of pertuzumab, trastuzumab, and docetaxel supports this regimen as the first-line therapy for patients with HER2-positive metastatic breast cancer from all geographic regions.
摘要
简介。本文按照地理区域对 III 期CLEOPATRA研究中的安全性数据进行了详细分析和报道。CLEOPATRA 研究是一项帕妥珠单抗、曲妥珠单抗和多西他赛作为一线药物治疗人表皮生长因子受体-2 (HER2) 阳性转移性乳腺癌的研究。
患者与方法。患者在周期 1 接受帕妥珠单抗/安慰剂的剂量为 840 mg，在后续周期中为 420 mg；曲妥珠单抗在周期 1 中的剂量为 8 mg/kg，在后续周期中为 6 mg/kg；多西他赛的初始剂量则为 75 mg/m2。所有研究药物均以静脉方式给药，每周 3 次。
结果。亚洲地区的患者将多西他赛的剂量减至 75 mg/m2 以下的几率 (47.0%) 高于其他地区的患者 (13.4%)，将多西他赛的剂量上调至 100 mg/m2 的几率 (2.4%) 则低于其他地区的患者 (18.7%)。亚洲患者的水肿（亚洲发生率为 26.1%，其他地区发生率为 5.4%）、肌痛 (42.3%, 14.7%)、指甲异常 (39.9%, 15.1%)、发热性中性粒细胞减少症 (18.6%, 7.1%)、上呼吸道感染 (25.7%, 10.2%)、食欲下降 (47.0%, 19.1%) 和皮疹 (44.3%, 22.0%) 的发生率至少为其他地区患者的两倍之多。不良事件并未导致亚洲患者的中位研究治疗周期数发生下降。按地区进行的疗效分析显示，与整个意向性治疗人群 (ITT)相比，风险比在无进展生存期（ITT：0.63；亚洲：0.68；其他地区：0.61）和总生存期（ITT：0.66；亚洲：0.64；其他地区：0.66）方面相似。
结论。虽然多西他赛在亚洲患者中的剂量减量发生率更高，但亚洲与其他地区的生存获益是相当的。帕妥珠单抗、曲妥珠单抗和多西他赛联合用药方案所表现出的良好风险-获益比表明，这一方案有资格成为所有地区 HER2 阳性转移性乳腺癌患者的一线治疗方案。
The Oncologist 2014;19:693–701
Keywords: Asia; Febrile neutropenia; HER2-positive metastatic breast cancer; Pertuzumab; Trastuzumab.
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