高选择性RET激酶抑制剂Selpercatinib （LOXO-292）治疗癌症患者的粘膜皮肤不良事件

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2025-01-07 DOI:10.1016/j.jtocrr.2025.100792

Rachel E. Reingold MD , Rose Parisi MD, MBA , Guilherme Harada MD , Andrea P. Moy MD , George Dranitsaris PhD , Jasmine H. Francis MD , Julia Canestraro OD, FAAO , Julia A. Lester MPH , Lauren A. Kaplanis RN , Dazhi Liu PharmD, BCOP , Mario E. Lacouture MD , Alexander Drilon MD

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引用次数: 0

摘要

选择性RET抑制剂被批准用于治疗RET依赖性癌症。尚未对粘膜皮肤不良事件（MAEs）进行全面表征；因此，我们鉴定了与选择性RET抑制剂selpercatinib相关的MAEs。方法我们评估了133例接受自泊卡替尼治疗的ret改变的癌症患者。确定MAEs的类型、分级、累积发生率和发病时间。本文描述了治疗中断、临床病理表现和治疗方法。比较有MAEs和无MAEs患者的实验室值。结果73例非小细胞肺癌（n = 46, 63%）、甲状腺髓样癌（n = 19, 26%）和甲状腺乳头状癌（n = 6, 8%）患者中，有126例主要为1/2级MAEs (n = 124, 98%)，其中48%报告≥1例MAE。口干（n = 49, 37%）、皮疹（n = 24, 18%）、眶周水肿（n = 16, 12%）和干燥（n = 12, 9%）是最常见的MAEs。所有级别MAEs的年累积发病率为55%，起始后至发病的中位时间为57天（四分位数范围：15-166）。MAEs组淋巴细胞百分比（平均21.8,SD = 11.3, p = 0.005）显著高于无MAEs组（16.9,SD = 10.0），免疫球蛋白E升高（平均275，SD = 294.5 IU/mL）。有18例（14%）与mae相关的治疗中断，包括以下情况：3例（2%）在维持剂量的情况下再次接受治疗，10例（7%）在剂量减少50%的情况下再次接受治疗，5例（4%）在剂量减少25%的情况下再次接受治疗，没有停药。为最常见的MAEs创建了一种治疗算法：用唾液和润滑剂治疗口干；粘膜炎用类固醇冲洗；外用类固醇伴或不伴外用乳酸铵的皮疹；冷敷或咖啡因敷眶周水肿；用润肤剂治疗干燥和瘙痒。结论选择性RET抑制与MAE的独特特征有关。早期识别和管理MAEs可以改善生活质量，减少中断，并最大限度地提高治疗效益。

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Mucocutaneous Adverse Events in Patients With Cancer Treated with the Highly Selective RET Kinase Inhibitor Selpercatinib (LOXO-292)

Introduction

Selective RET inhibitors are approved for the treatment of RET-dependent cancers. A comprehensive characterization of mucocutaneous adverse events (MAEs) has not been performed; therefore, we characterized MAEs associated with the selective RET inhibitor, selpercatinib.

Methods

We assessed 133 patients with RET-altered cancers treated with selpercatinib. The type, grade, cumulative incidence, and time to onset of MAEs were determined. Therapy interruptions, clinicopathologic findings, and management were described. Laboratory values were compared between patients with and without MAEs.

Results

A total of 73 patients with mostly NSCLC (n = 46, 63%), medullary thyroid (n = 19, 26%), and papillary thyroid (n = 6, 8%) cancers had 126 predominantly grade 1/2 (n = 124, 98%) MAEs, with 48% reporting greater than one MAE. Xerostomia (n = 49, 37%), rash (n = 24, 18%), periorbital edema (n = 16, 12%), and xerosis (n = 12, 9%) were the most common MAEs. The yearly cumulative incidence of all-grade MAEs was 55%, with a median time to onset of 57 (interquartile range: 15–166) days after initiation. Those with MAEs had a significantly higher percentage of lymphocytes (mean = 21.8, SD = 11.3, p = 0.005) compared with those without MAEs (16.9, SD = 10.0) and elevated immunoglobulin E (mean = 275, SD = 294.5 IU/mL). There were 18 (14%) MAE-related therapy interruptions, including the following: three (2%) rechallenged with dose maintained, 10 (7%) with a 50% dose reduction, 5 (4%) with a 25% dose reduction, and no drug discontinuations. A treatment algorithm was created for the most common MAEs: xerostomia managed with saliva and lubricants; mucositis with steroid rinses; rashes with topical steroids with or without topical ammonium lactate; periorbital edema with cold or caffeine compresses; and xerosis and pruritus with emollients.

Conclusions

Selective RET inhibition is associated with a unique MAE profile. Early recognition and management of MAEs may improve quality of life, minimize interruptions, and maximize therapeutic benefit.

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