Weekly Paclitaxel/Carboplatin/Trastuzumab Therapy Improves Pathologic Complete Remission in Aggressive HER2-Positive Breast Cancers, Especially in Luminal-B Subtype, Compared With a Once-Every-3-Weeks Schedule
Weekly Paclitaxel/Carboplatin/Trastuzumab Therapy Improves Pathologic Complete Remission in Aggressive HER2-Positive Breast Cancers, Especially in Luminal-B Subtype, Compared With a Once-Every-3-Weeks Schedule
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与每 3 周一次的治疗方案相比，每周一次的紫杉醇/卡铂/曲妥珠单抗治疗可改善侵袭性 HER2 阳性乳腺癌（尤其是 Luminal-B 亚型）的病理完全缓解。
DOI：
10.1634/theoncologist.2012-0057
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发表时间：
2013-05-01
期刊：
影响因子：
5.8
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
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作者：
Yu, Ke-Da;Liu, Guang-Yu;Shao, Zhi-Ming
背景在这项II期试验中，评估了紫杉醇、卡铂和曲妥珠单抗（PCarH）两种不同方案治疗HER2阳性、局部侵袭性（IIB-IIIC期）乳腺癌的疗效和耐受性。患者被随机分配接受每周一次（16周内12次给药）或每3周一次（12周内4次给药）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定的35% pCR绝对差异，每组至少需要26例可评估患者（双侧α = 0.05，β = 0.2）。共入组56例患者（每周一次组，n = 29;每3周一次组，n = 27）。在意向治疗分析中，在31例患者中发现乳房/腋窝的pCR（55%; 95%置信区间[CI]：41%-69%）。与每3周一次给药方案相比，每周一次给药获得了更高的pCR（41% vs. 69%; p = 0.03）。在调整临床和病理因素后，每周一次给药比每3周一次给药更有效，风险比为0.3（95% CI：0.1 - 0.9; p = 0.03）。有趣的是，每周一次给药在lumina I-B（HER2阳性）和ERBB 2+肿瘤中均导致高pCR率（67% vs. 71%; p =.78），而与ERBB 2+肿瘤相比，lumina I-B（HER2阳性）肿瘤从每3周一次给药方案中获益较少（21% vs. 62%，p =.03）。这些结果在多变量调整后仍然存在，表明每周给药在Luminal-B（HER2阳性）亚组中更有效（p = 0.02），但在ERBB 2+亚组中无效（p = 0.50）。更频繁的给药可能会提高根除乳腺和腋窝浸润性癌症的可能性，特别是在管腔B（HER2阳性）亚型中。进一步的研究来验证我们的发现是必要的。
Background. 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.Methods. 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 alpha = 0.05, beta = 0.2).Results. 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 lumina I-B (HER2-positive) and ERBB2+ tumors (67% vs. 71%; p = .78), whereas lumina I-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).Conclusion. 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.