在LIBRETTO-001项目中,色瑞替尼治疗转染过程中RET激活的晚期实体瘤的长期安全性:随着时间推移不良事件的不同模式。

IF 4.8 2区 医学 Q1 ONCOLOGY
Oncologist Pub Date : 2024-12-06 DOI:10.1093/oncolo/oyae282
Luis E Raez, Ashish C Massey, Scott S Barker, Patrick M Peterson, Katherine Liming, Nathan A Pennell
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引用次数: 0

摘要

背景赛乐替尼是一种选择性RET抑制剂,已被批准用于治疗RET激活的癌症。不良事件(AEs)可通过调整剂量加以控制。这项事后分析描述了LIBRETTO-001安全人群长期随访后舍培卡替尼的临床安全性概况:LIBRETTO-001是一项正在进行的I/II期单臂开放标签试验(NCT03157128)。符合条件的患者年龄≥18岁,诊断为晚期/转移性RET融合阳性实体瘤、RET突变甲状腺髓样癌或其他RET激活肿瘤。在I期治疗中,患者接受舍帕替尼20毫克QD或20-240毫克BID治疗;在II期治疗中,患者接受160毫克BID治疗。分析人群包括所有接受过≥1次舍培卡替尼治疗并随访至数据截止日(2023年1月13日)的患者:837名患者的中位随访时间为45.4个月(95% CI,44.5-46.6);中位治疗时间为30.1个月(0.1-66.8)。76.2%的患者出现了≥3级的治疗突发 AEs(TEAEs);最常见的事件是高血压(19.7%)、ALT 升高(11.8%)和低钠血症(9.2%)。51.4%的患者报告了严重的 TEAEs。最常报告的任何等级的 AEs 在 "结论 "中:舍帕替尼的长期治疗是可行的。通过调整剂量可以控制AEs,使大多数患者能够继续安全地接受治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Long-term safety of selpercatinib for Rearranged during transfection (RET)-activated advanced solid tumors in LIBRETTO-001: differing patterns of adverse events over time.

Background: Selpercatinib is a selective RET inhibitor approved for treatment of RET-activated cancers. Adverse events (AEs) are manageable with dose modifications. This post hoc analysis characterized selpercatinib's clinical safety profile after long-term follow-up in the safety population of LIBRETTO-001.

Patients and methods: LIBRETTO-001 is an ongoing phase I/II, single-arm, open-label trial (NCT03157128). Eligible patients were ≥18 years old with diagnosis of advanced/metastatic RET fusion-positive solid tumor, RET-mutant medullary thyroid cancer, or other RET-activated tumors. In phase I, patients received selpercatinib 20 mg QD or 20-240 mg BID; patients in phase II received 160 mg BID. The analyzed population comprised all patients who received ≥1 selpercatinib dose and were followed up until data cutoff (January 13, 2023).

Results: For the 837 patients, median follow-up was 45.4 months (95% CI, 44.5-46.6); median time on treatment was 30.1 months (range 0.1-66.8). Grade ≥3 treatment-emergent AEs (TEAEs) were reported in 76.2% of patients; most common events were hypertension (19.7%), ALT increased (11.8%), and hyponatremia (9.2%). Serious TEAEs were reported in 51.4% of patients. Most frequently reported any-grade AEs at <6 months of treatment were fatigue (36.6%), dry mouth (32.8%), and ALT increased (30.5%); at ≥24 months of treatment, these were edema (63.2%), diarrhea (60.7%), and fatigue (53.0%). Selpercatinib-related TEAEs leading to reduced dosage were reported in 39.3%, those leading to treatment interruption were reported in 47.1%, and those leading to discontinuation were reported in 4.3% of patients.

Conclusion: Long-term treatment with selpercatinib is feasible. AEs are manageable with dose modifications, allowing most patients to continue safely on therapy.

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来源期刊
Oncologist
Oncologist 医学-肿瘤学
CiteScore
10.40
自引率
3.40%
发文量
309
审稿时长
3-8 weeks
期刊介绍: The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.
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