Cui Wanyuan, Franchini Fanny, Alexander Marliese, Officer Ann, Wong Hui-Li, IJzerman Maarten, Desai Jayesh, Solomon Benjamin J
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.
University of Melbourne, Centre for Health Policy and Centre for Cancer Research, Melbourne, VIC, 3000, Australia.
Lung Cancer. 2020 Aug;146:310-317. doi: 10.1016/j.lungcan.2020.06.030. Epub 2020 Jun 26.
KRAS mutations are found in 20-30 % of non-small cell lung cancers (NSCLC) and were traditionally considered undruggable. KRAS mutation confers sensitivity to KRAS covalent inhibitors, however its prognostic impact remains unclear. This study assesses the frequency, clinical features, prevalence of brain metastases and outcomes in KRAS NSCLC in a real-world setting.
Patients enrolled in the prospective Thoracic Malignancies Cohort (TMC) between July 2012 to October 2019 with recurrent/metastatic non-squamous NSCLC, available KRAS results, and without EGFR/ALK/ROS1 gene aberrations, were selected. Data was extracted from TMC and patient records. Clinicopathologic features, treatment and overall survival (OS) was compared for KRAS wildtype (KRAS) and KRAS mutated (KRAS); and KRAS and other (KRAS) mutations.
Of 1386 NSCLC patients, 1040 were excluded: non-metastatic/recurrent (526); unknown KRAS status (356); ALK/EGFR/ROS1 positive (154); duplicate (4). Of 346 patients analysed, 144 (42 %) were KRAS, of whom 65 (45 %) were KRAS. All patients with KRAS were active or ex-smokers, compared to 92 % of KRAS and 83 % of KRAS. The prevalence of brain metastases during follow-up was similar between KRAS and KRAS (33 % vs 40 %, p = 0.17), and KRAS and KRAS (40 % vs 41 %, p = 0.74). The proportion of patients receiving one or multiple lines of systemic therapy was comparable. OS was similar between KRAS and KRAS (p = 0.54), and KRAS and KRAS (p = 0.39).
Patients with KRAS and KRAS, and KRAS and KRAS NSCLC have comparable clinical features, treatment and survival. While not prognostic, KRAS may be an important predictive biomarker as promising KRAS covalent inhibitors continue to be developed.
KRAS 突变见于 20%-30% 的非小细胞肺癌（NSCLC），传统上被认为是不可靶向治疗的。KRAS 突变使肿瘤对 KRAS 共价抑制剂敏感，但其预后影响仍不明确。本研究评估了真实世界中 KRAS 突变型 NSCLC 的发生频率、临床特征、脑转移发生率及预后情况。
选取 2012 年 7 月至 2019 年 10 月期间纳入前瞻性胸部恶性肿瘤队列（TMC）的复发性/转移性非鳞状 NSCLC 患者，其 KRAS 检测结果可用，且无 EGFR/ALK/ROS1 基因畸变。数据从 TMC 和患者记录中提取。比较 KRAS 野生型（KRAS）和 KRAS 突变型（KRAS）；以及 KRAS 与其他（KRAS）突变的临床病理特征、治疗情况和总生存期（OS）。
1386 例 NSCLC 患者中，1040 例被排除：非转移性/复发性（526 例）；KRAS 状态未知（356 例）；ALK/EGFR/ROS1 阳性（154 例）；重复病例（4 例）。在分析的 346 例患者中，144 例（42%）为 KRAS 野生型，其中 65 例（45%）为 KRAS 突变型。所有 KRAS 突变型患者均为现吸烟者或既往吸烟者，而 KRAS 野生型患者中这一比例为 92%，其他（KRAS）突变患者中为 83%。随访期间，KRAS 野生型与 KRAS 突变型患者脑转移发生率相似（33% 对 40%，p = 0.17），KRAS 与其他（KRAS）突变患者脑转移发生率也相似（40% 对 41%，p = 0.74）。接受一线或多线全身治疗的患者比例相当。KRAS 野生型与 KRAS 突变型患者的 OS 相似（p = 分0.54），KRAS 与其他（KRAS）突变患者的 OS 也相似（p = 0.39）。
KRAS 野生型与 KRAS 突变型、KRAS 与其他（KRAS）突变的 NSCLC 患者具有相似的临床特征、治疗情况和生存期。虽然 KRAS 突变不是预后指标，但随着有前景的 KRAS 共价抑制剂不断研发，KRAS 突变可能是一个重要的预测生物标志物。
