Impact of KRAS G12D subtype and concurrent pathogenic mutations on advanced non-small cell lung cancer outcomes.

Autor: Caballé-Perez E; Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.; Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico., Hernández-Pedro N; Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico., Ramos-Ramírez M; Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico., Barrios-Bernal P; Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico., Romero-Núñez E; Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico., Lucio-Lozada J; Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico., Ávila-Ríos S; Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico., Reyes-Terán G; Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico., Cardona AF; Thoracic Oncology Unit and Direction of Research, Science and Education, Luis Carlos Sarmiento Angulo, Cancer Treatment and Research Center (CTIC), Bogotá, Colombia.; Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia.; Molecular Oncology and Biology Systems Research Group (Fox-G), Universidad El Bosque, Bogotá, Colombia., Arrieta O; Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico. ogar@unam.mx.; Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico. ogar@unam.mx.
Jazyk: angličtina
Zdroj: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico [Clin Transl Oncol] 2024 Apr; Vol. 26 (4), pp. 836-850. Date of Electronic Publication: 2023 Jul 25.
DOI: 10.1007/s12094-023-03279-2
Abstrakt: Purpose: Mutations in the Kirsten rat sarcoma viral (KRAS) oncogene constitute a significant driver of lung adenocarcinoma, present in 10-40% of patients, which exhibit heterogeneous clinical outcomes, mainly driven by concurrent genetic alterations. However, characterization of KRAS mutational subtypes and their impact on clinical outcomes in Latin America is limited.
Methods: A cohort study was conducted at the National Cancer Institute (INCan) of Mexico. Individuals with advance-staged of adenocarcinoma and KRAS mutations, detected by next-generation sequencing, having undergone at least one line of therapy were included for analysis. Clinical and pathological characteristics were retrieved from institutional database from June 2014 to March 2023.
Results: KRAS was identified in fifty-four (15.6%) of 346 patients, among which 50 cases were included for analysis. KRAS G12D (n = 16, 32%) and KRAS G12C (n = 16, 32%) represented the most prevalent subtypes. KRAS G12D mutations were associated with female (p = 0.018), never smokers (p = 0.108), and concurrences with EGFR (25.0% vs. 17.6%, p = 0.124) and CDKN2A (18.8% vs. 14.7%, p = 0.157). KRAS G12D patients showed a better ORR (66.6% vs. 30.0%; OR 4.66, 95% CI 1.23-17.60, p = 0.023) and on multivariate analysis was significantly associated with better PFS (HR 0.36, 95% CI 0.16-0.80; p = 0.012) and OS (HR 0.24, 95% CI 0.08-0.70; p = 0.009).
Conclusions: To our knowledge, this study represents the first effort to comprehensively characterize the molecular heterogeneity of KRAS-mutant NSCLC in Latin American patients. Our data reinforce the current view that KRAS-mutated NSCLC is not a single oncogene-driven disease and emphasizes the prognostic impact of diverse molecular profiles in this genomically defined subset of NSCLC. Further validation is warranted in larger multicenter Latin American cohorts to confirm our findings.
(© 2023. The Author(s).)
Databáze: MEDLINE
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