Abstract：
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.
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.
摘要：
最近FDA加速批准索托拉西，一种高选择性KRASG12C抑制剂，为KRASp.（G12C）突变的非鳞状非小细胞肺癌（NSCLC）的治疗提供了新的机会。本研究的目的是确定荷兰IV期非鳞NSCLC中KRAS突变的患病率，以揭示即将到来的KRAS靶向治疗的潜在影响。
2013年、2015年和2017年在荷兰诊断为IV期非鳞状NSCLC的所有患者均通过全国荷兰癌症登记处（NCR）和荷兰病理学登记处（PALGA）进行选择。从病理报告中检索人口统计学和病理变量，包括性别，年龄,KRAS突变状态,使用的分子测试方法，和其他基因的突变状态。
密码子12/13/61/146中任何KRAS突变的患病率为39.1%。在所有非鳞状NSCLC病例的15.5％中检测到KRASp。（G12C），占所有KRAS突变病例的39.6％。国家对KRAS突变的检测率从2013年的70％增加到2017年的82％。随着时间的推移，测试技术随着下一代测序作为2017年主要使用的方法(71.6%)而发生了显著变化，但随着时间的推移并不影响KRAS突变的患病率。当KRAS作为更大面板的一部分进行测试时，KRASp.(G12C)突变常与TP53(47.7%)或STK11(10.3%)同时发生突变.
KRASp.(G12C)的高患病率为15%的IV期非鳞状细胞肺癌患者提供了一种有希望的新的特异性治疗选择。
2013年、2015年和2017年在荷兰诊断为IV期非鳞状NSCLC的所有患者均通过全国荷兰癌症登记处（NCR）和荷兰病理学登记处（PALGA）进行选择。从病理报告中检索人口统计学和病理变量，包括性别，年龄,KRAS突变状态,使用的分子测试方法，和其他基因的突变状态。
密码子12/13/61/146中任何KRAS突变的患病率为39.1%。在所有非鳞状NSCLC病例的15.5％中检测到KRASp。（G12C），占所有KRAS突变病例的39.6％。国家对KRAS突变的检测率从2013年的70％增加到2017年的82％。随着时间的推移，测试技术随着下一代测序作为2017年主要使用的方法(71.6%)而发生了显著变化，但随着时间的推移并不影响KRAS突变的患病率。当KRAS作为更大面板的一部分进行测试时，KRASp.(G12C)突变常与TP53(47.7%)或STK11(10.3%)同时发生突变.
KRASp.(G12C)的高患病率为15%的IV期非鳞状细胞肺癌患者提供了一种有希望的新的特异性治疗选择。
