National Center for Tumor Diseases (NCT) Heidelberg, Germany.
Department of Gynaecology and Obstetrics, Clinic Frankfurt-Hoechst, Germany.
Eur J Cancer. 2019 Jan;106:181-192. doi: 10.1016/j.ejca.2018.10.015. Epub 2018 Dec 5.
GeparOcto compared efficacy and safety of two chemotherapy regimens in high-risk early breast cancer (BC): sequential treatment with intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin (M, Myocet®) with additional carboplatin (PM(Cb)) in triple-negative BC (TNBC).
Patients with cT1c-cT4a-d and centrally assessed human epidermal growth factor receptor (HER)2-positive BC or TNBC were eligible, irrespective of nodal status, luminal B-like tumours only if pN+. Patients were randomised (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m) followed by P (225 mg/m) followed by C (2000 mg/m), each q2w for 3 cycles or weekly P (80 mg/m) plus M (20 mg/m) plus, in TNBC, Cb (area under curve (AUC) 1.5). HER2-positive BC patients additionally received trastuzumab (6 [loading dose 8]mg/kg q3w) and pertuzumab (420 [840]mg q3w) with all P and C cycles. Primary end-point was pathological complete response (pCR, ypT0/is ypN0), secondary end-points included other pCR definitions, pCR in stratified subpopulations, tolerability and compliance. This trial is registered with ClinicalTrials.gov number NCT02125344.
945/961 randomised patients started treatment. The median age was 48 years; 7.6% had cT3-4, 46% cN+, 66% G3, 40% HER2-positive, 43% TNBC. pCR rate with iddEPC was 48.3%, with PM(Cb) 48.0%, respectively (PM(Cb) versus iddEPC odds ratio 0.99; 95% confidence interval 0.77-1.28, P = 0.979) with no significant differences observed in TNBC, HER2-positive, luminal B-like subtypes. 16.4% with iddEPC and 34.1% with PM(Cb) discontinued treatment (P < 0.001), mainly due to adverse events; two patients on PM(Cb) died.
In high-risk early BC there is no difference in pCR rates following neoadjuvant treatment with iddEPC or weekly PM(Cb), respectively. iddEPC is one of the effective dose-dense regimens feasible in daily practice.
GeparOcto 比较了两种化疗方案在高危早期乳腺癌（BC）中的疗效和安全性：密集剂量表柔比星、紫杉醇和环磷酰胺（iddEPC）序贯治疗和每周紫杉醇联合非聚乙二醇化脂质体阿霉素（M，Myocet®）加额外卡铂（PM（Cb））在三阴性乳腺癌（TNBC）中的应用。
符合条件的患者为 cT1c-cT4a-d 和中央评估人表皮生长因子受体（HER）2 阳性 BC 或 TNBC，无论淋巴结状态如何，仅在 luminal B-like 肿瘤 pN+时才符合条件。患者按 BC 亚型、Ki67、淋巴细胞优势 BC 分层随机分配（n=961）接受 18 周 E（150mg/m），随后 P（225mg/m），随后 C（2000mg/m），每 2 周 1 次，共 3 个周期，或每周 P（80mg/m）加 M（20mg/m），在 TNBC 中加 Cb（AUC 1.5）。HER2 阳性 BC 患者还接受曲妥珠单抗（6[负荷剂量 8]mg/kg q3w）和帕妥珠单抗（420[840]mg q3w），与所有 P 和 C 周期一起使用。主要终点是病理完全缓解（pCR，ypT0/is ypN0），次要终点包括其他 pCR 定义、分层亚组的 pCR、耐受性和依从性。该试验在 ClinicalTrials.gov 登记号 NCT02125344。
945/961 名随机患者开始治疗。中位年龄为 48 岁；7.6%为 cT3-4，46%为 cN+，66%为 G3，40%为 HER2 阳性，43%为 TNBC。iddEPC 的 pCR 率为 48.3%，PM（Cb）为 48.0%（PM（Cb）与 iddEPC 的比值比为 0.99；95%置信区间为 0.77-1.28，P=0.979），在 TNBC、HER2 阳性、luminal B-like 亚型中未见显著差异。iddEPC 组有 16.4%的患者和 PM（Cb）组有 34.1%的患者停止治疗（P<0.001），主要是由于不良事件；PM（Cb）组有 2 例患者死亡。
在高危早期 BC 中，接受密集剂量表柔比星或每周 PM（Cb）新辅助治疗后的 pCR 率无差异。iddEPC 是一种在日常实践中可行的有效密集剂量方案之一。
