PO.CL09.02 · 临床研究

KRAS G12D突变非小细胞肺癌患者的真实世界结局：加州大学健康数据仓库回顾性分析

Real world outcomes for patients with KRAS G12D -mutated non-small cell lung cancer: A University of California Health Data Warehouse retrospective analysis

编号 6637 展板 6 时间 4/21 02:00–05:00 区域 Section 47 主讲 Jingtong Liang, No Degree

分会场 Real World Data to Provide Real World Evidence

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作者与单位 Authors & Affiliations

Jingtong Liang¹, Tali Azenkot², Sandip Patel²

¹Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles - UCLA, Los Angeles, CA,²University of California San Diego - Moores Cancer Center, San Diego, CA

摘要 Abstract

中文摘要

背景：KRAS是非小细胞肺癌（NSCLC）中最常见的驱动突变，G12C和G12D是其最常见的点突变之一。与KRAS G12C相比，KRAS G12D突变患者更可能是从不吸烟者，且对免疫检查点抑制剂（ICI）的应答更差。随着KRAS G12D靶向疗法正在研发中，有必要更深入地了解当前标准治疗相关的真实世界结局。方法：我们在加州大学健康数据仓库中回顾性分析了有和无KRAS突变的NSCLC患者。估计一线ICI的治疗时间（ToT），ICI相关总生存期（OS）定义为从首次ICI输注至死亡或失访的时间。应用Kaplan-Meier分析、Cox比例风险模型和学生t检验。结果：我们识别出3,391例NSCLC患者，包括158例（5%）KRAS G12D患者和735例（22%）其他KRAS突变患者。患者诊断时中位（范围）年龄为64（20-89）岁，57%为女性（见表）。在接受ICI的842例患者（25%）中，58%接受pembrolizumab治疗，20%接受nivolumab（含5%联合ipilimumab），8%接受atezolizumab或durvalumab。与其他KRAS突变患者相比，KRAS G12D中西班牙裔患者更多（20对36例，p < 0.01）。在Cox模型中校正年龄、种族和民族后，KRAS G12D患者的ICI ToT（4.3对4.8个月；p = 0.25；HR，95%CI：1.30，0.83-2.04）和ICI相关OS（9.4对14.0个月；p = 0.36；HR，95%CI：1.23，0.79-1.92）与其他KRAS突变患者相似。结论：借助结构化、多中心数据集合的力量，我们描述了KRAS G12D突变NSCLC患者的真实世界结局。表. 患者特征。KRAS G12D NSCLC患者（n=158） KRAS 非G12D NSCLC患者（n=735） P值全部NSCLC患者（n=3391）性别女性 95（60%） 431（59%） 0.798 1932（57%）男性 63（40%） 304（41%） 1458（43%）诊断时年龄中位（范围） 67（24-86） 61（24-89） 64（20-89）民族西班牙裔 20（13%） 36（5%） <0.001 259（8%）非西班牙裔 136（86%） 665（90%） 2994（88%）未知 2（1%） 34（5%） 138（4%）种族亚裔 100（63%） 512（70%） <0.01 1934（57%）黑人/非裔美国人 4（3%） 44（6%） 144（4%）白人 25（16%） 95（13%） 896（26%）其他 26（16%） 56（4%） 325（10%）未知 3（2%） 28（7%） 92（3%）吸烟从不吸烟 10（6%） 36（5%） 0.2337 342（10%）既往吸烟 8（5%） 56（8%） 189（6%）经常吸烟 1（1%） 20（2%） 40（1%）未知 139（88%） 623（85%） 2820（83%） ICI ToT（月）中位 4.3 4.8 0.25 ICI相关OS（月）中位 9.4 14.0 0.36

查看英文原文 English abstract

Background: KRAS is the most common driver mutation in non-small cell lung cancer (NSCLC), with G12C and G12D among its most frequent point mutations. Patients with KRAS G12D mutations are more likely to be never-smokers with worse response to immune checkpoint inhibitors (ICI) compared to those with KRAS G12C . As KRAS G12D -targeted therapies are under development, a greater understanding of real-world outcomes associated with current standard-of-care treatments is warranted. Methods : We retrospectively analyzed NSCLC patients with and without KRAS mutations in the University of California Health Data Warehouse. Time on treatment (ToT) of first-line ICIs was estimated, and ICI-related overall survival (OS) was defined as the time from the first ICI infusion until death or loss to follow up. Kaplan-Meier analysis, Cox proportional hazards model, and student's t-test were applied. Results : We identified 3,391 NSCLC patients, including 158 patients (5%) with KRAS G12D , and 735 (22%) with other KRAS mutations. Patients had a median (range) age of 64 (20-89) upon diagnosis and 57% were female (Table). Among 842 patient (25%) who received ICIs, 58% were treated with pembrolizumab, 20% with nivolumab (including 5% with ipilimumab), and 8% with either atezolizumab or durvalumab. Compared to patients with other KRAS mutations, there were more Hispanic patients with KRAS G12D (20 versus 36 patients, p < 0.01). When adjusting for age, race, and ethnicity in a Cox model, patients with KRAS G12D had similar ToT of ICIs (4.3 versus 4.8 months; p = 0.25; HR, 95%CI: 1.30, 0.83-2.04) and ICI-related OS (9.4 versus 14.0 months; p = 0.36; HR, 95%CI: 1.23, 0.79 - 1.92) as those with other KRAS mutations. Conclusion : Harnessing the power of a structured, multicenter data collective, we describe real-world outcomes from patients with KRAS G12D -mutated NSCLC. Table. Patient Characteristics. KRAS G12D NSCLC patients (n=158) KRAS NON-G12D NSCLC patients (n=735) P value All NSCLC patients (n=3391) Sex Female 95 (60%) 431 (59%) 0.798 1932 (57%) Male 63 (40%) 304 (41%) 1458 (43%) Age at diagnosis Median (range) 67 (24-86) 61 (24-89) 64 (20-89) Ethnicity Hispanic 20 (13%) 36 (5%) <0.001 259 (8%) Non-Hispanic 136 (86%) 665 (90%) 2994 (88%) Unknown 2 (1%) 34 (5%) 138 (4%) Race Asian 100 (63%) 512 (70%) <0.01 1934 (57%) Black/African American 4 (3%) 44 (6%) 144 (4%) White 25 (16%) 95 (13%) 896 (26%) Others 26 (16%) 56 (4%) 325 (10%) Unknown 3 (2%) 28 (7%) 92 (3%) Smoking Never smoker 10 (6%) 36 (5%) 0.2337 342 (10%) Former smoker 8 (5%) 56 (8%) 189 (6%) Regular smoker 1 (1%) 20 (2%) 40 (1%) Unknown 139 (88%) 623 (85%) 2820 (83%) ICI ToT (months) Median 4.3 4.8 0.25 ICI-related OS (months) Median 9.4 14.0 0.36

利益披露 Disclosure

J. Liang, None.. T. Azenkot, None.. S. Patel, None.

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