Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Lung Cancer. 2024 Aug;194:107898. doi: 10.1016/j.lungcan.2024.107898. Epub 2024 Jul 25.
KRAS mutations, particularly KRAS, are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRAS-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 KRAS-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 KRAS-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. KRAS-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 KRAS-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 KRAS-targeted therapies.
KRAS 突变，尤其是 KRAS，在非小细胞肺癌（NSCLC）中很常见。免疫检查点抑制剂（ICIs）一直是一线治疗方法，但最近开发的 KRAS 选择性抑制剂，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，以深入了解接受 ICIs 治疗后接受系统治疗的 KRAS 阳性晚期 NSCLC 患者的真实世界治疗模式和结局。
从加拿大罕见分子改变篮子真实世界观察研究（CARMA-BROS）中，分析了来自 9 个加拿大中心的 102 名 KRAS 阳性晚期 NSCLC 患者的队列，这些患者于 2015 年至 2021 年间确诊。临床人口统计学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%为女性；99%为当前/既往吸烟；59%PD-L1≥50%），在接受 ICIs 后表现出不同的治疗模式。大多数患者将 ICIs 作为一线治疗，随后的治疗线包括化疗和靶向治疗。在接受 ICIs 后接受系统治疗的患者中，中位总生存期为 12.6 个月，真实世界无进展生存期为 4.7 个月。接受 ICIs 后接受 KRAS 选择性靶向治疗（n=20）的患者与接受单药化疗的患者相比，真实世界无进展生存期更长（aHR=0.39，p=0.012）。
本研究为 KRAS 阳性晚期 NSCLC 接受 ICIs 治疗后的真实世界数据做出了贡献。在接受 ICIs 治疗后缺乏标准的治疗顺序，突显了在不断发展的 KRAS 靶向治疗领域中进一步研究和达成共识的必要性。
