Medical Oncology Department, Centre Léon Bérard, Lyon, France.
Medical Oncology Department Breast Care Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
Ann Oncol. 2019 May 1;30(5):766-773. doi: 10.1093/annonc/mdz061.
Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting.
In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8 mg/kg loading dose, then 6 mg/kg every 3 weeks (q3w)] and pertuzumab (840 mg loading dose, then 420 mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS).
Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54 years; 29% had received prior trastuzumab. Median treatment duration was 16 months for pertuzumab and trastuzumab and 4 months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1 months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%).
Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile.
CLINICALTRIALS.GOV: NCT01572038.
曲妥珠单抗联合帕妥珠单抗和多西他赛是 HER2 阳性转移性乳腺癌的标准一线治疗方法，这基于 III 期 CLEOPATRA 试验的结果。PERUSE 旨在评估在这种情况下研究者选择的紫杉烷类药物联合曲妥珠单抗和帕妥珠单抗的安全性和有效性。
在正在进行的多中心单臂 IIIb 期 PERUSE 研究中，患有不可切除的 HER2 阳性晚期乳腺癌（局部复发性/转移性）（LR/MBC）且无既往 LR/MBC 全身治疗（除内分泌治疗外）的患者接受多西他赛、紫杉醇或nab-紫杉醇联合曲妥珠单抗[8mg/kg 负荷剂量，然后每 3 周（q3w）6mg/kg]和帕妥珠单抗（840mg 负荷剂量，然后 q3w 420mg），直到疾病进展或出现不可接受的毒性。主要终点是安全性。次要终点包括总缓解率（ORR）和无进展生存期（PFS）。
总体而言，1436 名患者接受了至少一剂治疗（最初有 775 名患者接受多西他赛，589 名患者接受紫杉醇，65 名患者接受 nab-紫杉醇）。中位年龄为 54 岁；29%的患者既往接受过曲妥珠单抗治疗。帕妥珠单抗和曲妥珠单抗的中位治疗持续时间为 16 个月，紫杉烷类药物的中位治疗持续时间为 4 个月。与多西他赛治疗相比，紫杉醇治疗相关的周围神经病变更多（所有级别周围神经病变 31%对 16%），但发热性中性粒细胞减少症（1%对 11%）和黏膜炎（14%对 25%）更少。在此次初步分析（52 个月的中位随访）中，总体中位 PFS 为 20.6 个月[95%置信区间（CI）18.9-22.7]（分别为多西他赛、紫杉醇和 nab-紫杉醇 19.6、23.0 和 18.1 个月）。ORR 为 80%（95%CI 78%-82%）（多西他赛 79%，紫杉醇 83%，nab-紫杉醇 77%）。
PERUSE 的初步结果表明，曲妥珠单抗、帕妥珠单抗和紫杉烷类药物一线治疗 HER2 阳性 LR/MBC 的安全性和疗效与 CLEOPATRA 试验结果一致。紫杉醇似乎是多西他赛的一种有效替代紫杉烷类药物，具有可预测的安全性，提供相似的 PFS 和 ORR。
临床试验.gov：NCT01572038。
