Neratinib是一种不可逆的全HER酪氨酸激酶抑制剂，已获批用于HER2阳性早期和转移性乳腺癌。腹泻是最常见的副作用，也是早期停药的最常见原因。II期CONTROL试验研究了抗腹泻预防或neratinib剂量递增(DE)预防腹泻。我们展示了完整的研究结果和两种DE策略的最终数据。完成曲妥珠单抗辅助治疗的患者口服240 mg/天的neratinib治疗1年。早期队列研究了必须服用loperamide的预防治疗，然后加用budesonide或colestipol。最终队列评估了neratinib在头2个(DE1)或4个(DE2)周期内的DE。主要终点是≥3级腹泻的发生率。通过FACT-B和EQ-5D-5L评估了与健康相关的生命质量(HRQoL)。共有563名患者分为六个队列。所有策略都降低了≥3级腹泻的发生率，其中DE1最低(DE1 13%; colestipol+loperamide [CL] 21%，DE2 27%; budesonide+loperamide [BL] 28%; loperamide [L] 31%; colestipol+loperamide随时使用 [CL-PRN] 33%) 。腹泻相关的停药很早就发生了，DE1最低(DE1 3%; CL 4%; DE2 6%; CL-PRN 8%; BL 11%; L 20%)。相对于历史对照组，更多的患者按规定期间服用了neratinib。使用pertuzumab不影响≥3级腹泻、腹泻相关停药或治疗持续时间的发生率。观察到HRQoL得分的早期短暂下降。这些来自CONTROL的完整结果表明，在治疗开始时积极管理可提高neratinib的耐受性。每两周配合需要服用loperamide的neratinib DE特别有效。NCT02400476。版权所有 ©2022作者。 由Elsevier Ltd.出版。保留所有权利。

Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for HER2-positive early-stage and metastatic breast cancer. Diarrhea is the most frequent side effect and the most common reason for early discontinuation. The phase II CONTROL trial investigated antidiarrheal prophylaxis or neratinib dose escalation (DE) for prevention of diarrhea. We present complete study results including final data for two DE strategies.Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year. Early cohorts investigated mandatory prophylaxis with loperamide, then additional budesonide or colestipol. Final cohorts assessed neratinib DE over the first 2 (DE1) or 4 weeks (DE2). The primary endpoint was incidence of grade ≥3 diarrhea. Health-related quality of life (HRQoL) was assessed using FACT-B and EQ-5D-5L.563 patients were enrolled into six cohorts. All strategies reduced grade ≥3 diarrhea with the lowest incidence in DE1 (DE1 13%; colestipol + loperamide [CL] 21%, DE2 27%; budesonide + loperamide [BL] 28%; loperamide [L] 31%; colestipol + loperamide as needed [CL-PRN] 33%). Diarrhea-related discontinuations occurred early and were lowest in DE1 (DE1 3%; CL 4%; DE2 6%; CL-PRN 8%; BL 11%; L 20%). More patients stayed on neratinib for the prescribed period versus historical controls. Prior pertuzumab use did not affect rates of grade ≥3 diarrhea, diarrhea-related discontinuations, or treatment duration. Early transient reductions in HRQoL scores were observed.These complete results from CONTROL show improved neratinib tolerability with proactive management at the start of therapy. Two-week neratinib DE with loperamide as needed was particularly effective.NCT02400476.Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.