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Shang-Gin Wu



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    P37 - Pathology - Biomarker Testing (ID 107)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P37.05 - Prognostic Characteristics and Immunotherapy Response of Non-Squamous NSCLC Patients with KRAS Mutation in East Asian Populations (ID 2313)

      00:00 - 00:00  |  Presenting Author(s): Shang-Gin Wu

      • Abstract
      • Slides

      Introduction

      Kras mutation is the most common driver oncogene present in non-small cell lung cancer (NSCLC) patients in Western countries. However, the incidence of Kras mutation in Asian patients is low. Recently, the precision medicine for Kras-mutated NSCLC patients has been under investigation. This study aimed to analyze the clinical characteristics and prognostic factors of patients with Kras-mutant NSCLC.

      Methods

      From 2005–2018, we collected non-squamous NSCLC tissue samples for Kras mutation analysis using direct Sanger sequencing or MassARRAY genotyping (SEQUENOM). Patients with Kras mutations were enrolled. Clinical characteristics, treatment course, time to tumor recurrence (TTR), and overall survival (OS) were analyzed using multivariate Cox models, to estimate adjusted hazard ratios (HR).

      Results

      Among 5278 non-squamous NSCLC patients, 249 (4.7%) had Kras mutations. After excluding 18 patients with double cancers, 231 were enrolled for the analysis. There were 159 (68.8%) males and 145 (61.9%) smokers. The major Kras mutation subtypes were G12C (31.8%), G12D (24%), and G12V (18.5%). Patients with Kras-G12C had a higher proportion of smokers (81.1%; p = 0.001). For the 87 early-stage (I–IIIa) patients, the difference in TTR among patients with G12C (22.8 months(mo)), G12D (41.3 mo), G12V (unmatured), and G12A/S/R/Other (114.8 mo) Kras mutation patterns was statistically significant (p = 0.040). For the 144 advanced-stage (IIIb/IV) patients, there was a borderline significant difference in OS among patients with G12C (7.7 mo), G12D (11.7 mo), G12V (5.2 mo), and G12A/S/R/Other (5.7 mo) Kras-mutation subtypes (p = 0.052). Multivariate analysis revealed association of shorter OS with stage IV disease status (HR: 2.08; p = 0.002), NSCLC-not otherwise specified histology (HR: 3.17; p = 0.040), and Kras-G12V (HR: 2.08; p = 0.022). About the treatment response of immune checkpoint inhibitors (ICIs), patients with Kras-G12C had a higher response rate (50% vs. 14.3%; p = 0.069) and longer progression-free survival (4.8 mo vs. 2.1 mo; p = 0.046) than those with Kras-non-G12C.

      Among the patients with Kras mutations, 8 (3.4%) patients had tumors with concomitant Kras- and EGFR mutations, including 4 deletion-19, 2 L858R, one G709V, and one G719S+E709A. Of them, 6 patients received EGFR TKI treatment (4 gefitinib and 2 erlotinib). The treatment responses were 3 partial response, 1 stable disease, and 2 progressive disease. In addition, co-mutation of ALK fusions (3[2.5%] of 122 patients studied), HER2 mutations (2[1.0%] of 210 patients) and BRAF mutation (1[0.5%] of 204 patients) were also detected.

      Conclusion

      Kras-G12C mutation was associated with shorter TTR in early-stage NSCLC patients, while Kras-G12V mutation was associated with shorter OS in advanced-stage patients. Kras-G12C was also associated with favorable ICIs treatment effectiveness.

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