Safety Implications of Switching Pembrolizumab Dosage From 200 mg Every 3 Weeks to 400 mg Every 6 Weeks in Patients With Advanced NSCLC
Safety Implications of Switching Pembrolizumab Dosage From 200 mg Every 3 Weeks to 400 mg Every 6 Weeks in Patients With Advanced NSCLC
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DOI：
10.1016/j.jtho.2022.06.010
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发表时间：
2022-10-01
影响因子：
20.4
通讯作者：
Ohe, Yuichiro
中科院分区：
文献类型：
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作者：
Higashiyama, Ryoko Inaba;Yoshida, Tatsuya;Ohe, Yuichiro
**引言**：基于模拟药代动力学建模及暴露 - 反应分析结果，每6周给予400毫克帕博利珠单抗（400毫克每6周一次，400 mg Q6W）的用药方案已获批。然而，治疗期间从每3周200毫克（200 mg Q3W）转换为400 mg Q6W的安全性仍不明确。
**方法**：本研究纳入了45例晚期非小细胞肺癌患者，2020年8月至2021年11月期间在我院将这些患者的帕博利珠单抗用药剂量从200 mg Q3W转换为400 mg Q6W。
**结果**：转换用药剂量时，患者的中位年龄为71岁（范围：32 - 84岁），32例患者（71.1%）为男性。转换前接受200 mg Q3W方案的中位周期数为6个（范围：1 - 31个）。转换后，45例患者中有17例（37.8%）在3个周期内出现新发或恶化的免疫相关不良事件（irAEs）。这些irAEs包括11例（24.4%）肺炎、3例（6.7%）腹泻、2例（4.4%）肾功能障碍、2例（4.4%）肾上腺功能障碍、1例（2.2%）皮疹、1例（2.2%）暴发性1型糖尿病。
**结论**：帕博利珠单抗用药剂量从200 mg Q3W转换为400 mg Q6W，即使是在之前接受200 mg Q3W方案治疗病情稳定的患者中，也会在早期周期出现新发或恶化的irAEs，尤其是肺炎。
（©2022国际肺癌研究协会。爱思唯尔公司出版。保留所有权利。）
Introduction: Administration of 400 mg pembrolizumab every 6 weeks (400 mg Q6W) has been approved on the basis of the results of simulated pharmacokinetic the weeks modeling and exposure-response analyses. Nevertheless, the safety of switching dosage from 200 mg every 3 weeks (Q3W) to 400 mg Q6W during treatment remains unclear.Methods: This study involved patients (N 1/4 45) with advanced NSCLC, in whom the pembrolizumab dosage was switched from 200 mg Q3W to 400 mg Q6W between August 2020 and November 2021 in our institute.Results: At the time of switching, the median age of the patients was 71 (range: 32-84) years, and 32 patients (71.1 %) were males. The median number of cycles of 200 mg Q3W before switching was six (range: 1-31). After switch-ing, new or worsening immune-related adverse events (irAEs) occurred in 17 of the 45 patients (37.8%) within three cycles. The irAEs were pneumonitis in 11 patients (24.4%), diarrhea in three patients (6.7%), renal dysfunc-tion in two patients (4.4%), adrenal dysfunction in two patients (4.4%), a skin rash in one patient (2.2%), fulminant type 1 diabetes mellitus in one patient (2.2%).Conclusions: The switching of pembrolizumab dosage from 200 mg Q3W to 400 mg Q6W resulted in the occurrence of new or worsening irAEs, in particular, pneumonitis, in the early cycles even in patients who had received stable treatment with 200 mg Q3W.(c) 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.