TBCRC 031：新辅助顺铂与多柔比星-环磷酰胺治疗HER2阴性乳腺癌胚系携带者的随机II期研究（INFORM试验）
TBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline Carriers With HER2-Negative Breast Cancer (the INFORM trial).
作者信息
Tung Nadine, Arun Banu, Hacker Michele R, Hofstatter Erin, Toppmeyer Deborah L, Isakoff Steven J, Borges Virginia, Legare Robert D, Isaacs Claudine, Wolff Antonio C, Marcom Paul Kelly, Mayer Erica L, Lange Paulina B, Goss Andrew J, Jenkins Colby, Krop Ian E, Winer Eric P, Schnitt Stuart J, Garber Judy E
机构信息
Beth Israel Deaconess Medical Center, Boston, MA.
The University of Texas MD Anderson Cancer Center, Houston, TX.
出版信息
J Clin Oncol. 2020 May 10;38(14):1539-1548. doi: 10.1200/JCO.19.03292. Epub 2020 Feb 25.
PURPOSE
Platinum compounds have activity in triple-negative breast cancer (TNBC) in germline mutation carriers ( carriers). Limited data exist for estrogen receptor (ER)-positive (+) breast cancer among carriers. INFORM is a randomized, multicenter, phase II trial comparing pathologic complete response (pCR) rates (ypT0/is, N0) after neoadjuvant single-agent cisplatin (CDDP) versus doxorubicin-cyclophosphamide (AC) in carriers with stage I-III human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Secondary objectives included residual cancer burden scores (RCB) of 0 or 1 (combined) and toxicity. The goal was to determine whether pCR was ≥ 20% higher with CDDP than AC.
PATIENTS AND METHODS
carriers with cT1-3 (≥ 1.5 cm), cN0-3 HER2-negative breast cancer were randomly assigned to preoperative CDDP (75 mg/m every 3 weeks × 4 doses) or AC (doxorubicin 60 mg/m; cyclophosphamide 600 mg/m every 2-3 weeks × 4 doses) followed by surgery. Pathologic responses were confirmed by central review.
RESULTS
A total of 118 patients were randomly assigned; 117 were included in outcome analyses. Mean age was 42 years (range, 24-73 years); 69% were +, 30% were +, and 2% had both mutations. Clinical stage was I for 19%, II for 63%, and III for 18%; 45% had nodal involvement at baseline. Seventy percent had TNBC. Clinical and tumor characteristics were well matched between treatment arms. The pCR rate was 18% with CDDP and 26% with AC, yielding a risk ratio (RR) of 0.70 (90% CI, 0.39 to 1.2). The risk of RCB 0 or 1 (RCB 0/1) was 33% with CDDP and 46% with AC (RR, 0.73; 90% CI, 0.50 to 1.1). Both regimens were generally well tolerated without unexpected toxicities.
CONCLUSION
pCR or RCB 0/1 is not significantly higher with CDDP than with AC in carriers with stage I-III HER2-negative breast cancer for both TNBC and ER+/HER2-negative disease.
目的
铂类化合物对携带种系突变的三阴性乳腺癌（TNBC）患者具有活性。关于携带种系突变的雌激素受体（ER）阳性（+）乳腺癌患者的数据有限。INFORM是一项随机、多中心、II期试验，比较新辅助单药顺铂（CDDP）与多柔比星-环磷酰胺（AC）用于I-III期人表皮生长因子受体2（HER2）阴性乳腺癌携带种系突变患者后的病理完全缓解（pCR）率（ypT0/is，N0）。次要目标包括残留癌负担评分为0或1（合并）以及毒性。目的是确定CDDP治疗的pCR率是否比AC高≥20%。
患者和方法
cT1-3（≥1.5 cm）、cN0-3 HER2阴性乳腺癌携带种系突变患者被随机分配接受术前CDDP（每3周75 mg/m²，共4剂）或AC（多柔比星60 mg/m²；环磷酰胺600 mg/m²，每2-3周1次，共4剂），随后进行手术。病理反应由中心审查确认。
结果
共118例患者被随机分配；117例纳入结果分析。平均年龄42岁（范围24-73岁）；69%为BRCA1+，30%为BRCA2+，2%两种突变均有。临床分期I期占19%，II期占63%，III期占18%；45%基线时有淋巴结受累。70%为TNBC。各治疗组之间的临床和肿瘤特征匹配良好。CDDP治疗的pCR率为18%，AC治疗的为26%，风险比（RR）为0.70（90%CI，0.39至1.2）。CDDP治疗的残留癌负担评分为0或1（RCB 0/1）的风险为33%，AC治疗的为46%（RR，0.73；90%CI，0.50至1.1）。两种方案总体耐受性良好，无意外毒性。
结论
对于TNBC和ER+/HER2阴性疾病的I-III期HER2阴性乳腺癌携带种系突变患者，CDDP治疗的pCR或RCB 0/1并不显著高于AC治疗。
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