在 2 期和 3 期乳腺癌新辅助治疗中，个体水平病理完全缓解与无事件生存和远处无复发生存的相关性：I-SPY2 适应性随机临床试验的 3 年随访分析。
Association of Event-Free and Distant Recurrence-Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer: Three-Year Follow-up Analysis for the I-SPY2 Adaptively Randomized Clinical Trial.
机构信息
Masonic Cancer Center, University of Minnesota, Minneapolis.
Perelman School of Medicine, University of Pennsylvania, Philadelphia.
出版信息
JAMA Oncol. 2020 Sep 1;6(9):1355-1362. doi: 10.1001/jamaoncol.2020.2535.
IMPORTANCE
Pathologic complete response (pCR) is a known prognostic biomarker for long-term outcomes. The I-SPY2 trial evaluated if the strength of this clinical association persists in the context of a phase 2 neoadjuvant platform trial.
OBJECTIVE
To evaluate the association of pCR with event-free survival (EFS) and pCR with distant recurrence-free survival (DRFS) in subpopulations of women with high-risk operable breast cancer treated with standard therapy or one of several novel agents.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter platform trial of women with operable clinical stage 2 or 3 breast cancer with no prior surgery or systemic therapy for breast cancer; primary tumors were 2.5 cm or larger. Women with tumors that were ERBB2 negative/hormone receptor (HR) positive with low 70-gene assay score were excluded. Participants were adaptively randomized to one of several different investigational regimens or control therapy within molecular subtypes from March 2010 through 2016. The analysis included participants with follow-up data available as of February 26, 2019.
INTERVENTIONS
Standard-of-care neoadjuvant therapy consisting of taxane treatment with or without (as control) one of several investigational agents or combinations followed by doxorubicin and cyclophosphamide.
MAIN OUTCOMES AND MEASURES
Pathologic complete response and 3-year EFS and DRFS.
RESULTS
Of the 950 participants (median [range] age, 49 [23-77] years), 330 (34.7%) achieved pCR. Three-year EFS and DRFS for patients who achieved pCR were both 95%. Hazard ratios for pCR vs non-pCR were 0.19 for EFS (95% CI, 0.12-0.31) and 0.21 for DRFS (95% CI, 0.13-0.34) and were similar across molecular subtypes, varying from 0.14 to 0.18 for EFS and 0.10 to 0.20 for DRFS.
CONCLUSIONS AND RELEVANCE
The 3-year outcomes from the I-SPY2 trial show that, regardless of subtype and/or treatment regimen, including 9 novel therapeutic combinations, achieving pCR after neoadjuvant therapy implies approximately an 80% reduction in recurrence rate. The goal of the I-SPY2 trial is to rapidly identify investigational therapies that may improve pCR when validated in a phase 3 confirmatory trial. Whether pCR is a validated surrogate in the sense that a therapy that improves pCR rate can be assumed to also improve long-term outcome requires further study.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01042379.
重要性
病理完全缓解（pCR）是长期预后的已知预后生物标志物。I-SPY2 试验评估了在 2 期新辅助平台试验的背景下，这种临床相关性是否仍然存在。
目的
评估在接受标准治疗或几种新型药物治疗的高危可手术乳腺癌女性亚组中，pCR 与无事件生存（EFS）和 pCR 与远处无复发生存（DRFS）之间的关联。
设计、地点和参与者：多中心平台试验，纳入无手术或乳腺癌全身治疗史的可手术临床 2 期或 3 期乳腺癌女性；原发肿瘤直径≥2.5cm。排除 ERBB2 阴性/激素受体（HR）阳性且 70 基因检测评分低的肿瘤患者。根据分子亚型，参与者接受适应性随机分组，接受几种不同的研究方案或对照治疗，研究时间为 2010 年 3 月至 2016 年。分析包括截至 2019 年 2 月 26 日有随访数据的参与者。
干预措施
标准新辅助治疗包括紫杉烷治疗加或不加（对照组）几种研究药物或联合治疗，然后加用多柔比星和环磷酰胺。
主要结果和测量
病理完全缓解和 3 年 EFS 和 DRFS。
结果
在 950 名参与者中（中位[范围]年龄，49[23-77]岁），330 名（34.7%）达到 pCR。pCR 患者的 3 年 EFS 和 DRFS 均为 95%。pCR 与非 pCR 患者的 EFS 和 DRFS 风险比分别为 0.19（95%CI，0.12-0.31）和 0.21（95%CI，0.13-0.34），且在分子亚型之间相似，EFS 为 0.14-0.18，DRFS 为 0.10-0.20。
结论和相关性
I-SPY2 试验的 3 年结果表明，无论亚型和/或治疗方案如何，包括 9 种新型治疗联合方案，新辅助治疗后达到 pCR 意味着复发率降低约 80%。I-SPY2 试验的目的是快速识别可能在 3 期确证性试验中提高 pCR 的研究治疗方法。pCR 是否是一个经过验证的替代终点，即提高 pCR 率的治疗方法可以假设也能提高长期预后，这需要进一步研究。
试验注册
ClinicalTrials.gov 标识符：NCT01042379。
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