Garcia Betzabel N Cajiao, van Kempen Léon C, Kuijpers Chantal C H J, Schuuring Ed, Willems Stefan M, van der Wekken Anthonie J
University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.
Foundation PALGA, Houten, The Netherlands.
Lung Cancer. 2022 May;167:1-7. doi: 10.1016/j.lungcan.2022.03.015. Epub 2022 Mar 24.
The recent accelerated FDA approval of sotorasib, a highly selective KRAS G12C inhibitor, offers new opportunities for the treatment of KRAS p.(G12C)-mutated non-squamous non-small cell lung cancer (NSCLC). The objective of the current study was to the determine the prevalence of KRAS mutations in stage IV non-squamous NSCLC in The Netherlands to reveal the potential impact of upcoming KRAS targeted therapy.
All patients diagnosed with stage IV non-squamous NSCLC in 2013, 2015 and 2017 in the Netherlands were selected by linking the nation-wide Netherlands Cancer Registry (NCR) and the Dutch Pathology Registry (PALGA). Demographic and pathological variables were retrieved from the pathology reports including sex, age, KRAS mutation status, molecular test method used, and the mutation status of other genes.
Prevalence for any KRAS mutations in codon 12/13/61/146 was 39.1%. KRAS p.(G12C) was detected in 15.5% of all non-squamous NSCLC cases representing 39.6% of all KRAS-mutant cases. National testing rate for KRAS mutations increased from 70% in 2013 to 82% in 2017. Testing techniques changed significantly over time with next generation sequencing as the main used method in 2017 (71.6%) but did not affect prevalence of KRAS mutations over time. When KRAS was tested as part of a larger panel, the KRAS p.(G12C) mutation was frequently reported with a concurrent mutation in TP53 (47.7%) or STK11 (10.3%).
The high prevalence for KRAS p.(G12C) offers a promising new specific treatment option for 15% of all stage IV non-squamous NSCLC patients.
近期美国食品药品监督管理局（FDA）加速批准了高选择性KRAS G12C抑制剂索托拉西布，为治疗KRAS p.(G12C)突变的非鳞状非小细胞肺癌（NSCLC）提供了新机遇。本研究的目的是确定荷兰IV期非鳞状NSCLC中KRAS突变的发生率，以揭示即将到来的KRAS靶向治疗的潜在影响。
通过将全国性的荷兰癌症登记处（NCR）和荷兰病理学登记处（PALGA）相链接，选取2013年、2015年和2017年在荷兰被诊断为IV期非鳞状NSCLC的所有患者。从病理报告中获取人口统计学和病理学变量，包括性别、年龄、KRAS突变状态、使用的分子检测方法以及其他基因的突变状态。
密码子12/13/61/146中任何KRAS突变的发生率为39.1%。在所有非鳞状NSCLC病例中，15.5%检测到KRAS p.(G12C)，占所有KRAS突变病例的39.6%。KRAS突变的全国检测率从2013年的70%上升至2017年的82%。检测技术随时间显著变化，2017年主要使用的方法是二代测序（71.6%），但随着时间推移并未影响KRAS突变的发生率。当将KRAS作为更大检测 panel 的一部分进行检测时，KRAS p.(G12C)突变常伴有TP53（47.7%）或STK11（10.3%）的并发突变。
KRAS p.(G12C)的高发生率为15%的所有IV期非鳞状NSCLC患者提供了一种有前景的新的特异性治疗选择。
