Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)
Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)
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DOI：
10.1200/jco.2014.57.0572
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发表时间：
2015-01-01
影响因子：
45.3
通讯作者：
Winer, Eric P.
中科院分区：
文献类型：
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作者：
Sikov, William M.;Berry, Donald A.;Winer, Eric P.
三阴性乳腺癌（TNBC）患者中有三分之一的患者在标准新辅助化疗（NACT）后达到病理完全缓解（pCR）。CALGB 40603（Alliance），一项2 × 2析因、开放标签、随机II期试验，评估了添加卡铂和/或贝伐单抗的影响。患者和方法患有II至III期TNBC的患者（N = 443）接受紫杉醇80 mg/m2每周一次（wP）治疗12周，随后接受多柔比星加环磷酰胺每2周一次（ddAC）治疗4个周期，并随机分配至并行卡铂（曲线6下的面积），每3周一次，持续4个周期和/或贝伐单抗10 mg/kg，每2周一次，持续9个周期。加入这些药物对pCR乳腺癌（ypT 0/是），pCR乳腺癌/腋窝（ypT 0/isN 0），治疗交付和毒性的影响进行了analysed.ResultsPatients分配到卡铂或贝伐单抗不太可能完成wP和ddAC没有跳过剂量，剂量调整，或早期中止毒性。≥ 3级中性粒细胞减少症和血小板减少症在卡铂组更常见，贝伐单抗组高血压、感染、血栓栓塞事件、出血和术后并发症也更常见。采用单侧P值，添加卡铂（60% v 44%; P = 0.0018）或贝伐珠单抗（59% v 48%; P = 0.0089）显著增加pCR乳腺，而仅卡铂（54% v 41%; P = 0.0029）显著增加pCR乳腺/腋窝。两种药物之间的相互作用不能被证明。ConclusionIn阶段II至III TNBC，除了卡铂或贝伐单抗NACT增加pCR率，但这是否会改善无复发或总生存率是未知的。鉴于最近报道的辅助试验结果，不太可能进一步研究贝伐珠单抗在这种情况下的作用，但可以在确定性研究中评估卡铂的作用，理想情况下仅限于生物学定义的最有可能从这种药物中获益的患者亚群。(C)2014年美国临床肿瘤学会
PurposeOne third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 x 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab.Patients and MethodsPatients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m(2) once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed.ResultsPatients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade >= 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated.ConclusionIn stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent. (C) 2014 by American Society of Clinical Oncology