West German Study Group, Moenchengladbach, Germany.
Ev. Bethesda Hospital, Breast Center Niederrhein, Moenchengladbach, Germany.
J Clin Oncol. 2022 Aug 10;40(23):2557-2567. doi: 10.1200/JCO.21.02759. Epub 2022 Apr 11.
To our knowledge, WSG-ADAPT-HR+/HER2- (ClinicalTrials.gov identifier: NCT01779206; n = 5,625 registered) is the first trial combining the 21-gene expression assay (recurrence score [RS]) and response to 3-week preoperative endocrine therapy (ET) to guide systemic therapy in early breast cancer.
Baseline and postendocrine Ki67 (Ki67) were evaluated centrally. In the endocrine trial, all patients received exclusively ET: patients with pathologic regional lymph node status (pN) 0-1 (ie, 0-3 involved lymph nodes) entered control arm if RS ≤ 11 and experimental arm if RS12-25 with ET response (Ki67 ≤ 10%). All other patients (including N0-1 RS12-25 ET response) received dose-dense chemotherapy (CT) followed by ET in the CT trial. Primary end point of the endocrine trial was noninferiority of 5-year invasive disease-free survival (5y-iDFS) in experimental ( control) arm; secondary end points included distant DFS, overall survival, and translational research.
Intention-to-treat population comprised 2,290 patients (n = 1,422 experimental n = 868 control): 26.3% versus 34.6% premenopausal and 27.4% versus 24.0% pN1. One-sided 95% lower confidence limit of the 5y-iDFS difference was -3.3%, establishing prespecified noninferiority ( = .05). 5y-iDFS was 92.6% (95% CI, 90.8 to 94.0) in experimental versus 93.9% (95% CI, 91.8 to 95.4) in control arm; 5-year distant DFS was 95.6% versus 96.3%, and 5-year overall survival 97.3% versus 98.0%, respectively. Differences were similar in age and nodal subgroups. In N0-1 RS12-25, outcome of ET responders (ET alone) was comparable with that of ET nonresponders (CT) for age > 50 years and superior for age ≤ 50 years. ET response was more likely with aromatase inhibitors (mostly postmenopausal) than with tamoxifen (mostly premenopausal): 78.1% versus 41.1% ( < .001). ET response was 78.8% in RS0-11, 62.2% in RS12-25, and 32.7% in RS > 25 (n = 4,203, < .001).
WSG-ADAPT-HR+/HER2- demonstrates that guiding systemic treatment by both RS and ET response is feasible in clinical routine and spares CT in pre- and postmenopausal patients with ≤ 3 involved lymph nodes.
据我们所知，WSG-ADAPT-HR+/HER2-（临床试验.gov 标识符：NCT01779206；注册 5625 例）是首个将 21 基因表达检测（复发评分[RS]）和对 3 周术前内分泌治疗（ET）的反应结合起来指导早期乳腺癌系统治疗的试验。
对基线和内分泌 Ki67（Ki67）进行中心评估。在内分泌试验中，所有患者均接受单独 ET：病理区域淋巴结状态（pN）0-1（即 0-3 个受累淋巴结）的患者，如果 RS≤11，则进入对照组，如果 RS12-25 且 ET 反应（Ki67≤10%），则进入实验组；所有其他患者（包括 N0-1 RS12-25 ET 反应）在 CT 试验中接受密集化疗（CT）加 ET。内分泌试验的主要终点是实验组（对照组）5 年无侵袭性疾病生存率（5y-iDFS）的非劣效性；次要终点包括远处无病生存率、总生存率和转化研究。
意向治疗人群包括 2290 例患者（n=1422 例实验组 n=868 例对照组）：26.3%与 34.6%为绝经前，27.4%与 24.0%为 pN1。5y-iDFS 差异的单侧 95%置信下限为-3.3%，确定了预设的非劣效性（=0.05）。实验组 5y-iDFS 为 92.6%（95%CI，90.8 至 94.0），对照组为 93.9%（95%CI，91.8 至 95.4）；5 年远处无病生存率为 95.6%与 96.3%，5 年总生存率为 97.3%与 98.0%。在年龄和淋巴结亚组中，差异相似。在 N0-1 RS12-25 中，ET 反应者（仅 ET）的结局与 ET 无反应者（CT）相似，年龄＞50 岁的患者优于年龄≤50 岁的患者。芳香酶抑制剂（主要为绝经后）的 ET 反应率高于他莫昔芬（主要为绝经前）：78.1%与 41.1%（<0.001）。RS0-11 为 78.8%，RS12-25 为 62.2%，RS＞25 为 32.7%（n=4203，<0.001）。
WSG-ADAPT-HR+/HER2-表明，通过 RS 和 ET 反应指导系统治疗在临床常规中是可行的，可以避免≤3 个受累淋巴结的绝经前和绝经后患者接受 CT。
