伴发于考比替尼的浆液性视网膜病变的特征：四项研究的综合安全性分析。
Characterization of Serous Retinopathy Associated with Cobimetinib: Integrated Safety Analysis of Four Studies.
机构信息
Genentech, Inc. (a Member of the Roche Group), 1 DNA Way, South San Francisco, CA, USA.
F. Hoffmann-La Roche Ltd, Welwyn Garden City, UK.
出版信息
Drug Saf. 2022 Dec;45(12):1491-1499. doi: 10.1007/s40264-022-01248-2. Epub 2022 Oct 30.
INTRODUCTION AND OBJECTIVE
Serous retinopathy can be associated with MEK inhibitors, including cobimetinib. We present results of an integrated safety analysis to further characterize ocular functional and structural changes due to serous retinopathy.
METHODS
Four studies evaluating cobimetinib at the approved dose and schedule in combination with other oncology drugs were included. Study CO39721 incorporated standardized ophthalmologic assessments to fully characterize serous retinopathy events over time and was the primary study for analysis. Supporting information was provided by studies GO28141, WO29479, and GO30182.
RESULTS
In total, 655 patients received one or more doses of cobimetinib and comprised the safety-evaluable population. Overall, 117 patients (17.9%) had one or more serous retinopathy events, 24 (3.7%) had two or more events, and four (0.6%) had three or more events. Grade 3 events occurred in < 2.5% of patients. In CO39721, the median time to onset was 15 days (range 7-111); median time to resolution of first occurrence was 26 days (range 6-591 + days). Twelve of 25 patients (48.0%) recovered without a dose modification and 4/25 (16.0%) were recovered/recovering following a dose modification. The most frequent presentation of serous retinopathy was focal subretinal fluid on optical coherence tomography (62.8% of cases); in some instances (25.7% of cases), subretinal fluid was multifocal. There was no loss of visual function or visual acuity at serous retinopathy onset or resolution.
CONCLUSIONS
Results from this integrated safety analysis indicate that cobimetinib-associated serous retinopathy can be managed with or without a dose modification of cobimetinib at the discretion of the treating physician. No visual loss or permanent retinal damage was identified on comprehensive ophthalmologic assessments.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov identifiers: NCT03178851, NCT01689519, NCT02322814, and NCT02788279.
简介与目的
丝裂原活化细胞外信号调节激酶（MEK）抑制剂，包括考比替尼，可能会引起浆液性视网膜病变。我们报告了一项综合安全性分析的结果，以进一步描述因浆液性视网膜病变而导致的眼部功能和结构变化。
方法
纳入了四项评估考比替尼在批准剂量和方案下与其他肿瘤药物联合应用的研究。研究 CO39721 纳入了标准化的眼科评估，以全面描述随时间推移浆液性视网膜病变事件，并作为主要分析研究。GO28141、WO29479 和 GO30182 研究提供了补充信息。
结果
共有 655 例患者接受了一次或多次考比替尼治疗，构成了安全性评估人群。共有 117 例（17.9%）患者发生了 1 次或多次浆液性视网膜病变事件，24 例（3.7%）患者发生了 2 次或多次事件，4 例（0.6%）患者发生了 3 次或多次事件。3 级事件发生率<2.5%。在 CO39721 研究中，中位发病时间为 15 天（范围 7-111 天）；首次发生事件的中位缓解时间为 26 天（范围 6-591+天）。25 例患者中，12 例（48.0%）未经剂量调整即可恢复，4 例（16.0%）在调整剂量后可恢复/正在恢复。浆液性视网膜病变最常见的表现是光学相干断层扫描上的局灶性视网膜下积液（62.8%的病例）；在某些情况下（25.7%的病例），视网膜下积液为多灶性。浆液性视网膜病变发病或缓解时，视觉功能或视力均未丧失。
结论
这项综合安全性分析的结果表明，考比替尼相关的浆液性视网膜病变可通过考比替尼剂量调整或不调整来治疗，具体由治疗医生决定。全面的眼科评估未发现视觉丧失或永久性视网膜损伤。
临床试验注册
ClinicalTrials.gov 标识符：NCT03178851、NCT01689519、NCT02322814 和 NCT02788279。
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