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作者：SCI天天读
SCI
2 June 2023
Severe sotorasib-related hepatotoxicity and non-liver adverse events associated with sequential anti-PD(L)1 and sotorasib therapy in KRASG12C-mutant lung cancer
(Journal of Thoracic Oncology, IF: 20.121)
Ali Chour, Julie Denis, Céline Mascaux, Maeva Zysman, Laurence Bigay-Game, Aurélie Swalduz, Valérie Gounant, Alexis Cortot, Marie Darrason, Vincent Fallet, Edouard Auclin, Clémence Basse, Claire Tissot, Chantal Decroisette, Pierre Bombaron, Etienne Giroux-Leprieur, Luc Odier, Solenn Brosseau, Quentin Creusot, Marina Gueçamburu, Corentin Meersseman, Adrien Rochand, Adrien Costantini, Claire Marine Gaillard, Eric Wasielewski, Nicolas Girard, Jacques Cadranel, Claire Lafitte, Fanny Lebossé, Michael Duruisseaux
CORRESPONDENCE TO: michael.duruisseaux@chu-lyon.fr
Introduction 引言
Sequential anti-PD-(L)1 followed by small targeted therapy use is associated with increased prevalence of adverse events (AEs) in non-small cell lung cancer (NSCLC). KRASG12C inhibitor sotorasib may trigger severe immune-mediated hepatotoxicity when used in sequence or in combination with anti-PD-(L)1. This study was designed to address whether sequential anti-PD-(L)1 and sotorasib therapy increases the risk of hepatotoxicity and other AEs.
序贯抗PD-(L)1抗体治疗后进行小剂量靶向治疗与非小细胞肺癌（NSCLC）中不良事件（AEs）的发生率增加有关。KRASG12C抑制剂索托拉西布在序贯使用或与抗PD-(L)1联合使用时可能引发严重的免疫介导的肝毒性。本研究旨在探讨连续抗PD-(L)1和索托拉西布治疗是否会增加肝毒性和其他不良事件的风险。
Methods 方法
This is a multicenter, retrospective study of consecutive advanced KRASG12C-mutant NSCLC treated with sotorasib outside clinical trials in 16 French medical centers. Patient records were reviewed to identify sotorasib-related AEs (NCI-CTCAE v5.0). Grade 3 and higher AE was considered as severe. Sequence group was defined as patients who received an anti-PD-(L)1 as last line of treatment before sotorasib initiation and control group as patients who did not receive an anti-PD-(L)1 as last line of treatment before sotorasib initiation.
这是一项多中心、回顾性研究，对在16个法国医疗中心进行的非临床试验晚期KRASG12C突变型NSCLC患者进行索托拉西布治疗。对患者记录进行审查，以确定索托拉西布相关AE（NCI-TCAE v5.0）。3级及以上AE被视为严重AE。序贯治疗组被定义为在索托拉西布开始前接受抗PD-(L)1作为最末线治疗的患者，对照组被定义为在索托拉西布开始前未接受抗PD-(L)1作为最末线治疗的病人。
Results 结果
We identified 102 patients who received sotorasib, including 48 (47%) in sequence group and 54 (53%) in control group. Patients in control group received an anti-PD-(L)1 followed by at least one treatment regimen before sotorasib in 87% of the cases or did not receive an anti-PD-(L)1 at any time before sotorasib in 13% of the cases. Severe sotorasibrelated AEs were significantly more frequent in sequence group compared to control group (50% vs 13%, p<0.001). Severe sotorasib-related AEs occurred in 24 patients (24/48, 50%) in sequence group and among them 16 (67%) experienced a severe sotorasib-related hepatotoxicity. Severe sotorasib-related hepatotoxicity was three-fold more frequent in sequence group compared to control group (33% vs. 11%, p=0.006). No fatal sotorasib-related hepatotoxicity was reported. Non-liver severe sotorasib-related AEs were significantly more frequent in sequence group (27% vs 4%, p<0.001). Severe sotorasib-related AEs typically occurred in patients who received last anti-PD(L)1 infusion within 30 days before sotorasib initiation.
我们确定了102名接受索托拉西布治疗的患者，其中序贯治疗组48例（47%），对照组54例（53%）。对照组87%的患者在接受索托拉西布治疗前接受抗PD-(L)1治疗，并且曾经至少接受一种治疗方案，13%的患者在索托拉西布之前任何时候都没有接受抗PD-(L)1。与对照组相比，序贯治疗组中严重的索托拉西布相关AE的发生率明显更高（50%vs13%，p<0.001）。序贯治疗组中有24名患者（24/48，50%）发生了严重的索托拉西相关AEs，其中16名患者（67%）出现了严重的索托拉西布相关肝毒性。与对照组相比，序贯治疗组严重的索托拉西布相关肝毒性的发生率是对照组的三倍（33%对11%，p=0.006）。未报告致命的索托拉西布相关肝中毒。在序贯治疗组中，非肝脏严重的索托拉西布相关AE的发生率明显更高（27%对4%，p＜0.001）。严重的索托拉西布相关AE通常发生在接受索托拉西布治疗30天前曾接受最后一次抗PD-(L)1治疗的患者中。
Conclusions 结论
Sequential anti-PD-(L)1 and sotorasib therapy is associated with a significantly increased risk of severe sotorasib-related hepatotoxicity and severe non-liver AEs. We suggest avoiding starting sotorasib within 30 days from the last anti-PD-(L)1 infusion.
序贯抗PD-(L)1和索托拉西布治疗与严重索托拉西布相关肝毒性和严重非肝AE的风险显著增加有关。我们建议避免在最后一次抗PD-(L)1输注后30天内开始使用索托拉西布。
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原文地址：http://mp.weixin.qq.com/s?src=11×tamp=1685720868&ver=4566&signature=fZ7FT8Y3cmvhVgKOs5o6BiLQuHjiMQRzhlOgyqVQLx09SuT3OBfWgccq91knyJXhgo-S2cPVzt31SMUAsRwW3NE6gsu3ohChfAdsf3OjMmPzACS8KAEwU9hKi1Y0yL5L&new=1 |
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