Spring Laura M, Scarpetti Lauren, Medford Arielle J, Niemierko Andrzej, Comander Amy, Mulvey Therese, Schnipper Lowell, Isakoff Steven J, Moy Beverly, Wander Seth A, Shin Jennifer, Ephrem Zanta, Laposta Anneke R, Denault Elyssa, Abraham Elizabeth, Calistro Gayle, Kalashnikova Ekaterina, Rodriguez Angel, Liu Minetta C, Aleshin Alexey, Peppercorn Jeffrey, Ellisen Leif W, Bardia Aditya
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
NPJ Breast Cancer. 2025 Jan 7;11(1):2. doi: 10.1038/s41523-024-00708-5.
Optimal timing and dosing of adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitor in early breast cancer is controversial. This prospective phase II clinical trial investigated tolerability and safety of two ribociclib dosing schedules. Patients with stage I-III hormone receptor-positive (HR+)/HER2- breast cancer on adjuvant endocrine therapy (ET) were randomized to two ribociclib dosing schedules: 400 mg continuous vs 600 mg intermittent, with initiation in early (prior ET < 2 years) vs delayed (prior ET ≥ 2 years) setting. Primary objective was to evaluate safety and tolerability of continuous vs intermittent schedule. Primary endpoint was proportion of patients who discontinued ribociclib before completion of all 12 cycles (measured at 12 months). Recurrence free survival (RFS) and circulating tumor DNA (ctDNA) detection were also evaluated. 81 patients were enrolled. Only six serious adverse events occurred, with no significant difference between treatment arms and no subject deaths. Twenty-five patients (31%) discontinued ribociclib before completion of 12 months, with no significant difference between treatment arms. Ribociclib discontinuation was higher in early vs delayed initiation (36% vs 21%). At median follow-up of 20 months, two patients in the intermittent arm (600 mg; Arm 2) experienced disease recurrence (2-year RFS 97%, 95%CI 88-99%), vs none in the continuous arm (400 mg; Arm 1) (2-year RFS 100%). ctDNA was only identified in the two subjects with recurrent disease at median of 7.5 months prior to radiological recurrence. Ribociclib is a safe and well-tolerated adjunct to adjuvant ET in early-stage breast cancer. Delayed initiation of ribociclib at 400 mg continuous dosing was feasible, better tolerated and associated with promising outcomes. ctDNA detection preceded clinical evidence of recurrence and may be considered as a surveillance tool in breast cancer.
早期乳腺癌中辅助性细胞周期蛋白依赖性激酶（CDK）4/6抑制剂的最佳给药时间和剂量存在争议。这项前瞻性II期临床试验研究了两种瑞博西尼给药方案的耐受性和安全性。接受辅助内分泌治疗（ET）的I-III期激素受体阳性（HR+）/人表皮生长因子受体2阴性（HER2-）乳腺癌患者被随机分为两种瑞博西尼给药方案：400mg持续给药与600mg间歇给药，分别在早期（既往ET<2年）与延迟期（既往ET≥2年）开始给药。主要目的是评估持续给药方案与间歇给药方案的安全性和耐受性。主要终点是在完成所有12个周期之前停用瑞博西尼的患者比例（在12个月时测量）。还评估了无复发生存期（RFS）和循环肿瘤DNA（ctDNA）检测情况。共入组81例患者。仅发生6例严重不良事件，各治疗组之间无显著差异，也无受试者死亡。25例患者（31%）在12个月完成之前停用瑞博西尼，各治疗组之间无显著差异。早期开始给药时瑞博西尼停药率高于延迟开始给药（36%对21%）。在中位随访20个月时，间歇给药组（600mg；第2组）有2例患者出现疾病复发（2年RFS为97%，95%CI 88-99%），而持续给药组（第1组，400mg）无患者复发（2年RFS为100%）。ctDNA仅在2例复发疾病患者中检测到，中位时间为影像学复发前7.5个月。瑞博西尼是早期乳腺癌辅助内分泌治疗中一种安全且耐受性良好的辅助药物。400mg持续给药延迟开始使用瑞博西尼是可行的，耐受性更好且预后良好。ctDNA检测先于复发的临床证据，可被视为乳腺癌的一种监测工具。
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