TY - JOUR
T1 - Large-scale clinico-genomic profile of non-small cell lung cancer with KRAS G12C
T2 - Results from LC-SCRUM-Asia study
AU - Tamiya, Yutaro
AU - Matsumoto, Shingo
AU - Zenke, Yoshitaka
AU - Yoh, Kiyotaka
AU - Ikeda, Takaya
AU - Shibata, Yuji
AU - Kato, Terufumi
AU - Nishino, Kazumi
AU - Nakamura, Atsushi
AU - Furuya, Naoki
AU - Miyamoto, Shingo
AU - Kuyama, Shoichi
AU - Nomura, Shogo
AU - Ikeno, Takashi
AU - Udagawa, Hibiki
AU - Sugiyama, Eri
AU - Nosaki, Kaname
AU - Izumi, Hiroki
AU - Sakai, Tetsuya
AU - Hashimoto, Naozumi
AU - Goto, Koichi
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/2
Y1 - 2023/2
N2 - Introduction: KRAS G12C is an oncogenic driver mutation, accounting for approximately 14% of Caucasian patients with non-small cell lung cancer (NSCLC). Recently, several KRAS G12C-targeted drugs have been developed; however, the clinico-genomic characteristics of NSCLC patients with KRAS G12C remain unclear. Materials and Methods: Based on the large-scale prospective lung cancer genomic screening project (LC-SCRUM-Asia) database, the clinico-genomic characteristics and therapeutic outcomes of NSCLC patients with KRAS G12C were evaluated. Results: From March 2015 to March 2021, 10,023 NSCLC patients were enrolled in LC-SCRUM-Asia. KRAS mutations were detected in 1258 patients (14 %), including G12C in 376 (4.0 %), G12D in 289 (3.1 %) and G12V in 251 (2.7 %). The proportions of males and smokers were higher in patients with KRAS G12C than in those with KRAS non-G12C mutations (males: 73 % vs 63 %, p < 0.001; smokers: 89 % vs 76 %, p < 0.001). KRAS G12C-positive tumors showed a higher tumor mutation burden (TMB) (mean, 8.1 mut/Mb, p < 0.001) and a higher percentage of tumors with programmed cell death ligand-1 (PD-L1) expression ≥50 % (52 %, p = 0.08). The overall survival in patients with KRAS G12C (median, 24.6 months) was not different between patients with other mutation subtypes (G12V: 18.2 months, p = 0.23; G12D: 20.6 months, p = 0.65; other KRAS mutations: 18.3 months, p = 0.20). Among KRAS-mutated patients who received immune checkpoint inhibitors (ICIs), the progression-free survival in G12C-positive patients (median, 3.4 months) was similar to that in G12V-positive patients (4.2 months, p = 0.90), but significantly longer than that in G12D- (2.0 months, p = 0.02) and other KRAS mutation-positive patients (2.5 months, p = 0.02). Conclusions: The frequencies of KRAS G12C were lower in Asian than in Caucasian NSCLC patients. Among the KRAS-mutated NSCLC patients, G12C-positive tumors showed increased immunogenicity, such as high TMB and high PD-L1 expression, and potential sensitivity to ICIs.
AB - Introduction: KRAS G12C is an oncogenic driver mutation, accounting for approximately 14% of Caucasian patients with non-small cell lung cancer (NSCLC). Recently, several KRAS G12C-targeted drugs have been developed; however, the clinico-genomic characteristics of NSCLC patients with KRAS G12C remain unclear. Materials and Methods: Based on the large-scale prospective lung cancer genomic screening project (LC-SCRUM-Asia) database, the clinico-genomic characteristics and therapeutic outcomes of NSCLC patients with KRAS G12C were evaluated. Results: From March 2015 to March 2021, 10,023 NSCLC patients were enrolled in LC-SCRUM-Asia. KRAS mutations were detected in 1258 patients (14 %), including G12C in 376 (4.0 %), G12D in 289 (3.1 %) and G12V in 251 (2.7 %). The proportions of males and smokers were higher in patients with KRAS G12C than in those with KRAS non-G12C mutations (males: 73 % vs 63 %, p < 0.001; smokers: 89 % vs 76 %, p < 0.001). KRAS G12C-positive tumors showed a higher tumor mutation burden (TMB) (mean, 8.1 mut/Mb, p < 0.001) and a higher percentage of tumors with programmed cell death ligand-1 (PD-L1) expression ≥50 % (52 %, p = 0.08). The overall survival in patients with KRAS G12C (median, 24.6 months) was not different between patients with other mutation subtypes (G12V: 18.2 months, p = 0.23; G12D: 20.6 months, p = 0.65; other KRAS mutations: 18.3 months, p = 0.20). Among KRAS-mutated patients who received immune checkpoint inhibitors (ICIs), the progression-free survival in G12C-positive patients (median, 3.4 months) was similar to that in G12V-positive patients (4.2 months, p = 0.90), but significantly longer than that in G12D- (2.0 months, p = 0.02) and other KRAS mutation-positive patients (2.5 months, p = 0.02). Conclusions: The frequencies of KRAS G12C were lower in Asian than in Caucasian NSCLC patients. Among the KRAS-mutated NSCLC patients, G12C-positive tumors showed increased immunogenicity, such as high TMB and high PD-L1 expression, and potential sensitivity to ICIs.
KW - KRAS G12C
KW - KRAS mutation
KW - Next-generation sequencing
KW - Non-small cell lung cancer
KW - PD-L1 expression
KW - Tumor burden
UR - https://www.scopus.com/pages/publications/85146329661
UR - https://www.scopus.com/pages/publications/85146329661#tab=citedBy
U2 - 10.1016/j.lungcan.2022.12.019
DO - 10.1016/j.lungcan.2022.12.019
M3 - Article
C2 - 36634571
AN - SCOPUS:85146329661
SN - 0169-5002
VL - 176
SP - 103
EP - 111
JO - Lung Cancer
JF - Lung Cancer
ER -
