Prognostic Characteristics and Immunotherapy Response of Patients With Nonsquamous NSCLC With Kras Mutation in East Asian Populations: A Single-Center Cohort Study in Taiwan
Introduction: Kras mutation is the most common driver oncogene present in patients with NSCLC. Recently, the precision medicine for patients with Kras-mutated NSCLC has been under investigation, but the best treatment is still unknown. This study aimed to analyze the clinical characteristics, immune...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-02-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364320301910 |
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| author | Shang-Gin Wu, MD, PhD Wei-Yu Liao, MD, PhD Kang-Yi Su, PhD Sung-Liang Yu, PhD Yen-Lin Huang, MD Chong-Jen Yu, MD, PhD James Chih-Hsin Yang, MD, PhD Jin-Yuan Shih, MD, PhD |
| author_facet | Shang-Gin Wu, MD, PhD Wei-Yu Liao, MD, PhD Kang-Yi Su, PhD Sung-Liang Yu, PhD Yen-Lin Huang, MD Chong-Jen Yu, MD, PhD James Chih-Hsin Yang, MD, PhD Jin-Yuan Shih, MD, PhD |
| author_sort | Shang-Gin Wu, MD, PhD |
| collection | DOAJ |
| description | Introduction: Kras mutation is the most common driver oncogene present in patients with NSCLC. Recently, the precision medicine for patients with Kras-mutated NSCLC has been under investigation, but the best treatment is still unknown. This study aimed to analyze the clinical characteristics, immune checkpoint inhibitor (ICI) response, and prognostic factors of patients with NSCLC with different Kras mutation subtypes. Methods: From 2005 to 2018, we collected nonsquamous NSCLC tissue samples for Kras mutation analysis using direct Sanger sequencing or MassARRAY genotyping (Agena Bioscience, San Diego, CA) at the National Taiwan University Hospital. Clinical characteristics, ICI treatment effectiveness, time-to-tumor recurrence (TTR), and overall survival (OS) were analyzed using multivariate Cox models, to estimate adjusted hazard ratios (HRs). Results: Among 5278 patients with nonsquamous NSCLC, 246 (4.7%) had Kras mutations. The major Kras mutation subtypes were G12C (32.9%), G12D (23.7%), and G12V (18.9%). Patients with Kras-G12C had a higher proportion of male individuals (p = 0.018) and smokers (p < 0.001). Among the 25 patients treated with ICIs, patients with Kras-G12C had a higher response rate (53.8% versus 8.3%, p = 0.030) and longer progression-free survival (4.8 mo versus 2.1 mo, p = 0.028) than those with Kras-non-G12C. For the 85 patients with early-stage NSCLC, those with G12C had shorter TTR (22.8 mo) than those with Kras-non-G12C (97.7 mo, p = 0.004). For the 143 patients with advanced-stage NSCLC, there was a significant difference in OS between patients with Kras-G12C and Kras-non-G12C (7.7 mo versus 6.0 mo, p = 0.018) and patients with Kras-G12V had the shortest OS (5.2 mo). Multivariate analysis revealed association of shorter OS with Kras-G12V (HR = 2.47, p = 0.002), stage IV disease status (HR = 2.69, p = 0.008), and NSCLC—not otherwise specified histology (HR = 3.12, p = 0.002). Conclusions: Kras-G12C was associated with favorable ICI treatment effectiveness in patients with NSCLC. Kras-G12C mutation was associated with shorter TTR in patients with early-stage NSCLC, and Kras-G12V mutation was associated with shorter OS in patients with advanced-stage NSCLC when comparing with Kras-G12C. |
| first_indexed | 2024-12-16T14:34:46Z |
| format | Article |
| id | doaj.art-e57e98f289ae455ba7fe9760df585bcb |
| institution | Directory Open Access Journal |
| issn | 2666-3643 |
| language | English |
| last_indexed | 2024-12-16T14:34:46Z |
| publishDate | 2021-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj.art-e57e98f289ae455ba7fe9760df585bcb2022-12-21T22:28:08ZengElsevierJTO Clinical and Research Reports2666-36432021-02-0122100140Prognostic Characteristics and Immunotherapy Response of Patients With Nonsquamous NSCLC With Kras Mutation in East Asian Populations: A Single-Center Cohort Study in TaiwanShang-Gin Wu, MD, PhD0Wei-Yu Liao, MD, PhD1Kang-Yi Su, PhD2Sung-Liang Yu, PhD3Yen-Lin Huang, MD4Chong-Jen Yu, MD, PhD5James Chih-Hsin Yang, MD, PhD6Jin-Yuan Shih, MD, PhD7Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Cancer Center, National Taiwan University, Taipei, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, TaiwanDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, TaiwanDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pathology, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Pathology, National Taiwan University Hospital, Taipei, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, TaiwanDepartment of Oncology, National Taiwan University Cancer Center, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oncology, Cancer Research Center, National Taiwan University, Taipei, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan; Corresponding author: Address for correspondence: Jin-Yuan Shih, MD, PhD, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Rd, Taipei 100, Taiwan.Introduction: Kras mutation is the most common driver oncogene present in patients with NSCLC. Recently, the precision medicine for patients with Kras-mutated NSCLC has been under investigation, but the best treatment is still unknown. This study aimed to analyze the clinical characteristics, immune checkpoint inhibitor (ICI) response, and prognostic factors of patients with NSCLC with different Kras mutation subtypes. Methods: From 2005 to 2018, we collected nonsquamous NSCLC tissue samples for Kras mutation analysis using direct Sanger sequencing or MassARRAY genotyping (Agena Bioscience, San Diego, CA) at the National Taiwan University Hospital. Clinical characteristics, ICI treatment effectiveness, time-to-tumor recurrence (TTR), and overall survival (OS) were analyzed using multivariate Cox models, to estimate adjusted hazard ratios (HRs). Results: Among 5278 patients with nonsquamous NSCLC, 246 (4.7%) had Kras mutations. The major Kras mutation subtypes were G12C (32.9%), G12D (23.7%), and G12V (18.9%). Patients with Kras-G12C had a higher proportion of male individuals (p = 0.018) and smokers (p < 0.001). Among the 25 patients treated with ICIs, patients with Kras-G12C had a higher response rate (53.8% versus 8.3%, p = 0.030) and longer progression-free survival (4.8 mo versus 2.1 mo, p = 0.028) than those with Kras-non-G12C. For the 85 patients with early-stage NSCLC, those with G12C had shorter TTR (22.8 mo) than those with Kras-non-G12C (97.7 mo, p = 0.004). For the 143 patients with advanced-stage NSCLC, there was a significant difference in OS between patients with Kras-G12C and Kras-non-G12C (7.7 mo versus 6.0 mo, p = 0.018) and patients with Kras-G12V had the shortest OS (5.2 mo). Multivariate analysis revealed association of shorter OS with Kras-G12V (HR = 2.47, p = 0.002), stage IV disease status (HR = 2.69, p = 0.008), and NSCLC—not otherwise specified histology (HR = 3.12, p = 0.002). Conclusions: Kras-G12C was associated with favorable ICI treatment effectiveness in patients with NSCLC. Kras-G12C mutation was associated with shorter TTR in patients with early-stage NSCLC, and Kras-G12V mutation was associated with shorter OS in patients with advanced-stage NSCLC when comparing with Kras-G12C.http://www.sciencedirect.com/science/article/pii/S2666364320301910Kras mutationG12CLung cancerImmunotherapyPD-L1Concomitant mutation |
| spellingShingle | Shang-Gin Wu, MD, PhD Wei-Yu Liao, MD, PhD Kang-Yi Su, PhD Sung-Liang Yu, PhD Yen-Lin Huang, MD Chong-Jen Yu, MD, PhD James Chih-Hsin Yang, MD, PhD Jin-Yuan Shih, MD, PhD Prognostic Characteristics and Immunotherapy Response of Patients With Nonsquamous NSCLC With Kras Mutation in East Asian Populations: A Single-Center Cohort Study in Taiwan JTO Clinical and Research Reports Kras mutation G12C Lung cancer Immunotherapy PD-L1 Concomitant mutation |
| title | Prognostic Characteristics and Immunotherapy Response of Patients With Nonsquamous NSCLC With Kras Mutation in East Asian Populations: A Single-Center Cohort Study in Taiwan |
| title_full | Prognostic Characteristics and Immunotherapy Response of Patients With Nonsquamous NSCLC With Kras Mutation in East Asian Populations: A Single-Center Cohort Study in Taiwan |
| title_fullStr | Prognostic Characteristics and Immunotherapy Response of Patients With Nonsquamous NSCLC With Kras Mutation in East Asian Populations: A Single-Center Cohort Study in Taiwan |
| title_full_unstemmed | Prognostic Characteristics and Immunotherapy Response of Patients With Nonsquamous NSCLC With Kras Mutation in East Asian Populations: A Single-Center Cohort Study in Taiwan |
| title_short | Prognostic Characteristics and Immunotherapy Response of Patients With Nonsquamous NSCLC With Kras Mutation in East Asian Populations: A Single-Center Cohort Study in Taiwan |
| title_sort | prognostic characteristics and immunotherapy response of patients with nonsquamous nsclc with kras mutation in east asian populations a single center cohort study in taiwan |
| topic | Kras mutation G12C Lung cancer Immunotherapy PD-L1 Concomitant mutation |
| url | http://www.sciencedirect.com/science/article/pii/S2666364320301910 |
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