前瞻性WSG-ADAPT HR+/HER2-试验的导入期证明了一种研究设计的可行性，该设计将静态和动态生物标志物评估相结合，用于早期乳腺癌的个体化治疗。
The run-in phase of the prospective WSG-ADAPT HR+/HER2- trial demonstrates the feasibility of a study design combining static and dynamic biomarker assessments for individualized therapy in early breast cancer.
作者信息
Nitz Ulrike, Gluz Oleg, Kreipe Hans H, Christgen Matthias, Kuemmel Sherko, Baehner Frederick L, Shak Steven, Aktas Bahriye, Braun Michael, Lüdtke-Heckenkamp Kerstin, Forstbauer Helmut, Grischke Eva-Maria, Nuding Benno, Darsow Maren, Schumacher Claudia, Krauss Katja, Malter Wolfram, Thill Marc, Warm Mathias, Wuerstlein Rachel, Kates Ronald E, Harbeck Nadia
机构信息
West German Study Group, Moenchengladbach, Germany.
Medical College of Hannover, Institute for Pathology, Hannover, Germany.
出版信息
Ther Adv Med Oncol. 2020 Nov 23;12:1758835920973130. doi: 10.1177/1758835920973130. eCollection 2020.
BACKGROUND
Endocrine sensitivity, as determined by response of the proliferation marker Ki-67 to short-term preoperative endocrine therapy (ET), is currently not included in adjuvant treatment decisions in hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)- breast cancer (BC).
METHODS
The prospective WSG-ADAPT HR+/HER2- trial included patients with N0/N1 early BC who were candidates for adjuvant chemotherapy based on clinical-pathological criteria alone. The trial utilized a genomic assessment [the Recurrence Score (RS)] plus endocrine sensitivity testing to guide treatment. All patients received 3 (±1) weeks of preoperative induction ET. According to protocol, patients with RS 0-11 or RS 12-25 plus endocrine proliferation response (EPR, post-induction Ki-67 ⩽ 10%) were to be spared adjuvant chemotherapy.
RESULTS
The ADAPT HR+/HER2- trial run-in phase included 407 patients with baseline RS, of whom 386 (median age: 54 years) had complete data for Ki-67 at both baseline and post-induction. RS distribution: 23.1% RS 0-11, 58.3% RS 12-25, and 18.7% RS 26-100. EPR occurred in 84.3%, 76.0%, and 36.1% of these RS groups, respectively. Differences in EPR proportions (RS 26-100 others, RS 0-11 others) were significant (both < 0.001); Ki-67 quotients were higher for RS 26-100 ( = 0.02, Mann-Whitney). In premenopausal women ( = 146, mostly tamoxifen-treated), median quotient of Ki-67 level (post/pre) was significantly higher than in postmenopausal women ( = 222, mostly aromatase-inhibitor treated; 0.67 0.25, < 0.001). EPR was significantly associated with baseline estrogen-receptor status as determined by immunohistochemistry ( = 0.002) or real-time polymerase chain reaction ( < 0.001). Also, a strong correlation was observed between RS measured pre- and post-ET (R = 0.7, = 181).
CONCLUSIONS
This phase of the WSG-ADAPT HR+/HER2- trial confirms trial design estimates of RS and EPR. It indicates that the ADAPT concept of combining static and dynamic biomarker assessment for individualized therapy decisions in early BC is feasible using the EPR criterion post-induction Ki-67 ⩽ 10%.
CLINICALTRIALSGOV IDENTIFIER
NCT01779206.
背景
通过增殖标志物Ki-67对短期术前内分泌治疗（ET）的反应所确定的内分泌敏感性，目前未纳入激素受体（HR）阳性/人表皮生长因子受体2（HER2）阴性乳腺癌（BC）的辅助治疗决策中。
方法
前瞻性WSG-ADAPT HR+/HER2-试验纳入了仅根据临床病理标准适合辅助化疗的N0/N1期早期BC患者。该试验利用基因组评估[复发评分（RS）]加内分泌敏感性测试来指导治疗。所有患者接受3（±1）周的术前诱导ET。根据方案，RS为0-11或RS为12-25且内分泌增殖反应（EPR，诱导后Ki-67⩽10%）的患者可免于辅助化疗。
结果
ADAPT HR+/HER2-试验导入期纳入了407例有基线RS的患者，其中386例（中位年龄：54岁）在基线和诱导后均有完整的Ki-67数据。RS分布：23.1%的患者RS为0-11，58.3%的患者RS为12-25，18.7%的患者RS为26-100。这些RS组中EPR分别发生在84.3%、76.0%和36.1%的患者中。EPR比例的差异（RS为26-100组与其他组相比，RS为0-11组与其他组相比）具有显著性（均P<0.001）；RS为26-100组的Ki-67商更高（P=0.02，Mann-Whitney检验）。在绝经前女性（n=146，大多接受他莫昔芬治疗）中，Ki-67水平（诱导后/诱导前）的中位商显著高于绝经后女性（n=222，大多接受芳香化酶抑制剂治疗；0.67对0.25，P<0.001）。EPR与通过免疫组织化学（P=0.002）或实时聚合酶链反应（P<0.001）确定的基线雌激素受体状态显著相关。此外，ET前后测量的RS之间观察到强相关性（R=0.7，n=181）。
结论
WSG-ADAPT HR+/HER2-试验的这一阶段证实了RS和EPR的试验设计估计值。这表明，在早期BC中，使用诱导后Ki-67⩽10%的EPR标准，将静态和动态生物标志物评估相结合用于个体化治疗决策的ADAPT概念是可行的。
临床试验注册号
NCT01779206。
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