Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, China.
Oncologist. 2013;18(5):511-7. doi: 10.1634/theoncologist.2012-0057. Epub 2013 May 1.
The efficacy and tolerability of two different schedules of paclitaxel, carboplatin, and trastuzumab (PCarH) for HER2-positive, locally aggressive (stage IIB-IIIC) breast cancers were evaluated in this phase II trial.
Patients were randomly assigned to receive either weekly (12 doses over 16 weeks) or once-every-3-weeks (4 doses over 12 weeks) treatment. The primary endpoint was pathologic complete remission (pCR) in the breast and axilla. To detect an assumed 35% pCR absolute difference between the two schedules, a minimum of 26 assessable patients in each group was required (two-sided α = 0.05, β = 0.2).
A total of 56 patients were enrolled (weekly group, n = 29; every-3-weeks group, n = 27). In the intent-to-treat analysis, pCR in the breast/axilla were found in 31 patients (55%; 95% confidence interval [CI]: 41%-69%). Compared with the every-3-weeks schedule, the weekly administration achieved higher pCR (41% vs. 69%; p = .03). After adjustment for clinical and pathological factors, the weekly administration was more effective than the every-3-weeks schedule, with hazard ratio of 0.3 (95% CI: 0.1-0.9; p = .03). Interestingly, weekly administration resulted in high pCR rates in both luminal-B (HER2-positive) and ERBB2+ tumors (67% vs. 71%; p = .78), whereas luminal-B (HER2-positive) tumors benefited less from the every-3-weeks schedule compared with the ERBB2+ tumors (21% vs. 62%, p = .03). These results remain after multivariate adjustment, showing weekly administration was more effective in the luminal-B (HER2-positive) subgroup (p = .02) but not in the ERBB2+ subgroup (p = .50).
A more frequent administration might improve the possibility of eradicating invasive cancer in the breast and axilla, especially in the luminal-B (HER2-positive) subtype. Further studies to validate our findings are warranted.
本 II 期临床试验评估了曲妥珠单抗联合紫杉醇、卡铂不同方案（PCarH）用于治疗人表皮生长因子受体 2（HER2）阳性、局部侵袭性（ⅡB 期-ⅢC 期）乳腺癌的疗效和耐受性。
患者随机分配接受每周（16 周内 12 剂）或每 3 周（12 周内 4 剂）治疗。主要终点是乳腺和腋窝的病理完全缓解（pCR）。为了检测两种方案之间假设的 35%绝对 pCR 差异，每组需要至少 26 例可评估患者（双侧α=0.05，β=0.2）。
共纳入 56 例患者（每周组 29 例，每 3 周组 27 例）。意向治疗分析中，乳腺/腋窝 pCR 为 31 例（55%；95%置信区间[CI]：41%-69%）。与每 3 周方案相比，每周方案 pCR 更高（41% vs. 69%；p=0.03）。在校正临床和病理因素后，每周方案比每 3 周方案更有效，风险比为 0.3（95%CI：0.1-0.9；p=0.03）。有趣的是，每周方案在 luminal-B（HER2 阳性）和 ERBB2+肿瘤中均能达到较高的 pCR 率（67% vs. 71%；p=0.78），而 luminal-B（HER2 阳性）肿瘤从每 3 周方案中获益不及 ERBB2+肿瘤（21% vs. 62%；p=0.03）。这些结果在多变量调整后仍然存在，表明每周方案在 luminal-B（HER2 阳性）亚组中更有效（p=0.02），但在 ERBB2+亚组中无效（p=0.50）。
更频繁的给药可能会提高消除乳腺和腋窝浸润性癌症的可能性，特别是在 luminal-B（HER2 阳性）亚型中。需要进一步的研究来验证我们的发现。
