既往接受免疫检查点抑制剂治疗的 KRASG12C 阳性晚期 NSCLC 患者的治疗模式和结果：一项加拿大范围内的真实世界、多中心、回顾性队列研究。
Treatment patterns and outcomes in KRASG12C-positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study.
发表日期：2024 Aug
作者：
Samir H Barghout, Luna Jia Zhan, Starvroula Raptis, Faisal Al-Agha, Niki Esfahanian, Aimee Popovacki, Goulnar Kasymjanova, Francis Proulx-Rocray, Sze Wah Samuel Chan, Matthew Richardson, M Catherine Brown, Devalben Patel, Michelle Liane Dean, Vishal Navani, Erica Moore, Lane Carvery, Elizabeth Yan, Daniel Goldshtein, Jasmine Cleary-Gosine, Amanda Jw Gibson, Lynn Hubley, Karmugi Balaratnam, Tran Ngo, Azee Gill, Morgan Black, Adrian Sacher, Penelope A Bradbury, Frances A Shepherd, Natasha Leighl, Parneet Cheema, Sara Kuruvilla, Jason Agulnik, Shantanu Banerji, Rosalyn Juergens, Normand Blais, Winson Cheung, Paul Wheatley-Price, Geoffrey Liu, Stephanie Snow
来源：
LUNG CANCER
摘要：
KRAS 突变，特别是 KRASG12C，在非小细胞肺癌 (NSCLC) 中普遍存在。免疫检查点抑制剂 (ICIs) 一直是一线治疗方法，但最近开发的 KRASG12C 选择性抑制剂（例如 sotorasib）提供了新的治疗选择。我们进行了一项多中心回顾性队列研究，以深入了解 KRASG12C 阳性晚期 NSCLC 患者在 ICI 治疗后接受全身治疗的真实世界治疗模式和结果。来自加拿大癌症罕见分子改变篮真实世界观察研究 (CARMA-BROS) 对 2015 年至 2021 年间诊断的加拿大 9 个中心的 102 名 KRASG12C 阳性晚期 NSCLC 患者进行了分析。临床人口统计和治疗数据从电子健康记录中获得。使用 Kaplan-Meier 曲线和 Cox 比例风险模型评估生存结果。患者（中位年龄 66 岁；58% 女性；99% 当前/以前吸烟；59% PD-L1 ≥ 50%）在治疗后表现出异质性治疗模式-ICI。大多数患者接受 ICI 作为一线治疗，并接受不同的后续治疗，包括化疗和靶向治疗。在 ICI 后接受全身治疗的患者中，中位总生存期为 12.6 个月，实际无进展生存期为 4.7 个月。与单药化疗相比，ICI 后 KRASG12C 选择性靶向治疗 (n = 20) 显示出更长的真实世界无进展生存期 (aHR = 0.39，p = 0.012)。这项研究提供了有关 KRASG12C 阳性的宝贵真实世界数据ICI 治疗后的晚期 NSCLC。 ICI 后标准治疗测序的缺乏强调了在 KRASG12C 靶向疗法不断发展的前景中需要进一步调查和建立共识。版权所有 © 2024 Elsevier B.V. 保留所有权利。
KRAS mutations, particularly KRASG12C, are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRASG12C-selective inhibitors, such as sotorasib, present new therapeutic options. We conducted a multi-center retrospective cohort study to gain insights into real-world treatment patterns and outcomes in patients with KRASG12C-positive advanced NSCLC receiving systemic therapy post-ICI treatment.From the CAnadian CAncers With Rare Molecular Alterations-Basket Real-world Observational Study (CARMA-BROS), a cohort of 102 patients with KRASG12C-positive advanced NSCLC across 9 Canadian centers diagnosed between 2015 and 2021 was analyzed. Clinico-demographic and treatment data were obtained from electronic health records. Survival outcomes were assessed using Kaplan-Meier curves and Cox proportional hazards models.The patients (median age 66 years; 58 % female; 99 % current/former tobacco exposure; 59 % PD-L1 ≥ 50 %), exhibited heterogeneous treatment patterns post-ICI. Most patients received ICIs as a first-line therapy, with varying subsequent lines including chemotherapy and targeted therapy. In patients receiving systemic therapy post-ICI, median overall survival was 12.6 months, and real-world progression-free survival was 4.7 months. KRASG12C-selective targeted therapy post-ICI (n = 20) showed longer real-world progression-free survival compared to single-agent chemotherapy (aHR = 0.39, p = 0.012).This study contributes valuable real-world data on KRASG12C-positive advanced NSCLC post-ICI treatment. The absence of a standard treatment sequencing post-ICI underscores the need for further investigation and consensus-building in the evolving landscape of KRASG12C-targeted therapies.Copyright © 2024 Elsevier B.V. All rights reserved.