IMPORTANCE Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials. OBJECTIVE To compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival. DESIGN, SETTING, AND PARTICIPANTS The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence. Investigational treatments graduated in a prespecified subtype if there was 85% or greater predicted probability of higher rate of pathologic complete response (pCR) in a confirmatory, 300-patient, 1:1 randomized, neoadjuvant trial in that subtype. Evaluation of a secondary end point was reported from the 10 investigational agents tested in the I-SPY2 trial from March 200 through 2016, and analyzed as of September 9, 2020. The analysis plan included modeling of RCB within subtypes defined by hormone receptor (HR) and ERBB2 status and compared control treatments with investigational treatments that graduated and those that did not graduate. INTERVENTIONS Neoadjuvant paclitaxel plus/minus 1 of several investigational agents for 12 weeks, then 12 weeks of cyclophosphamide/doxorubicin chemotherapy followed by surgery. MAIN OUTCOMES AND MEASURES Residual cancer burden (pathological measure of residual disease) and event-free survival (EFS). RESULTS A total of 938 women (mean [SD] age, 49 [11] years; 66 [7%] Asian, 103 [11%] Black, and 750 [80%] White individuals) from the first 10 investigational agents were included, with a median follow-up of 52 months (IQR, 29 months). Event-free survival worsened significantly per unit of RCB in every subtype of breast cancer (HR-positive/ERBB2-negative: hazard ratio [HZR], 1.75; 95% CI, 1.45-2.16; HR-positive/ERBB2-positive: HZR, 1.55; 95% CI, 1.18-2.05; HR-negative/ERBB2-positive: HZR, 2.39; 95% CI, 1.64-3.49; HR-negative/ERBB2-negative: HZR, 1.99; 95% CI, 1.71-2.31). Prognostic information from RCB was similar from treatments that graduated (HZR, 2.00; 95% CI, 1.57-2.55; 254 [27%]), did not graduate (HZR, 1.87; 95% CI, 1.61-2.17; 486 [52%]), or were control (HZR, 1.79; 95% CI, 1.42-2.26; 198 [21%]). Investigational treatments significantly lowered RCB in HR-negative/ERBB2-negative (graduated and nongraduated treatments) and ERBB2-positive subtypes (graduated treatments), with improved EFS (HZR, 0.61; 95% CI, 0.41-0.93) in the exploratory analysis. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, the prognostic significance of RCB was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of RCB in addition to increasing pCR rate and appeared to improve EFS. Using a standardized quantitative method to measure response advances the interpretation of efficacy. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01042379.

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评估高危乳腺癌新辅助治疗中的残留癌症负担和无事件生存率：I-SPY2 随机临床试验数据分析。

重要性 残余癌症负担 (RCB) 分布可能会改善对新辅助乳腺癌试验疗效的解释。目的比较随机对照和研究性治疗在乳腺癌亚型中的 RCB 分布，并探讨其与生存率的关系。设计、设置和参与者 I-SPY2 是在美国开展的一项多中心、平台适应性、随机临床试验，按亚型比较研究性药物联合化疗与单独化疗对 2/3 期乳腺癌高危成年女性的疗效。早期复发的风险。如果在该亚型的 300 名患者、1:1 随机新辅助试验中，如果有 85% 或更高的病理完全缓解率 (pCR) 预测概率为 85% 或更高，则研究性治疗在该亚型中毕业。次要终点评估报告来自 200 年 3 月至 2016 年 I-SPY2 试验中测试的 10 种研究药物，并于 2020 年 9 月 9 日进行分析。分析计划包括在激素受体（HR ) 和 ERBB2 状态，并将对照治疗与已毕业和未毕业的研究性治疗进行比较。干预 新辅助紫杉醇加/减几种研究药物中的一种，持续 12 周，然后进行 12 周的环磷酰胺/多柔比星化疗，然后进行手术。主要结果和措施 残留癌症负担（残留疾病的病理学测量）和无事件生存期（EFS）。结果 共有 938 名女性（平均 [SD] 年龄，49 [11] 岁；66 [7%] 亚裔，103 [11%] 黑人，包括来自前 10 名研究人员的 750 [80%] 白人个体），中位随访时间为 52 个月（IQR，29 个月）。在每种乳腺癌亚型中，每单位 RCB 的无事件生存期显着恶化（HR 阳性/ERBB2 阴性：风险比 [HZR]，1.75；95% CI，1.45-2.16；HR 阳性/ERBB2 阳性：HZR ，1.55；95% CI，1.18-2.05；HR 阴性/ERBB2 阳性：HZR，2.39；95% CI，1.64-3.49；HR 阴性/ERBB2 阴性：HZR，1.99；95% CI，1.71-2.31 ）。RCB 的预后信息与已毕业（HZR，2.00；95% CI，1.57-2.55；254 [27%]）、未毕业（HZR，1.87；95% CI，1.61-2.17；486 [52%]）的治疗相似]），或为对照（HZR，1.79；95% CI，1.42-2.26；198 [21%]）。在探索性分析中，研究性治疗显着降低了 HR 阴性/ERBB2 阴性（分级和非分级治疗）和 ERBB2 阳性亚型（分级治疗）的 RCB，改善了 EFS（HZR，0.61；95% CI，0.41-0.93）。结论和相关性 在这项随机临床试验中，无论亚型和治疗如何，RCB 的预后意义都是一致的。有效的新辅助治疗除了增加 pCR 率外，还改变了 RCB 的分布，并且似乎改善了 EFS。使用标准化的定量方法来测量反应可以促进对疗效的解释。试验注册 ClinicalTrials.gov 标识符：NCT01042379。结论和相关性 在这项随机临床试验中，无论亚型和治疗如何，RCB 的预后意义都是一致的。有效的新辅助治疗除了增加 pCR 率外，还改变了 RCB 的分布，并且似乎改善了 EFS。使用标准化的定量方法来测量反应可以促进对疗效的解释。试验注册 ClinicalTrials.gov 标识符：NCT01042379。结论和相关性 在这项随机临床试验中，无论亚型和治疗如何，RCB 的预后意义都是一致的。有效的新辅助治疗除了增加 pCR 率外，还改变了 RCB 的分布，并且似乎改善了 EFS。使用标准化的定量方法来测量反应可以促进对疗效的解释。试验注册 ClinicalTrials.gov 标识符：NCT01042379。