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Título: | Associations of Tissue Tumor Mutational Burden and Mutational Status With Clinical Outcomes With Pembrolizumab Plus Chemotherapy Versus Chemotherapy For Metastatic NSCLC | Autores/as: | Garassino, Marina C. Gadgeel, Shirish Novello, Silvia Halmos, Balazs Felip, Enriqueta Speranza, Giovanna Hui, Rina Garon, Edward B. Horinouchi, Hidehito Sugawara, Shunichi Rodríguez Abreu, Delvys Reck, Martin Cristescu, Razvan Aurora-Garg, Deepti Loboda, Andrey Lunceford, Jared Kobie, Julie Ayers, Mark Piperdi, Bilal Pietanza, M. Catherine Paz-Ares, Luis |
Clasificación UNESCO: | 32 Ciencias médicas 320708 Hematología 320713 Oncología |
Palabras clave: | Lung Blockade Patterns Impact Kras, et al. |
Fecha de publicación: | 2023 | Publicación seriada: | JTO Clinical and Research Reports | Resumen: | Introduction: We evaluated tissue tumor mutational burden (tTMB) and mutations in STK11, KEAP1, and KRAS as biomarkers for outcomes with pembrolizumab plus platinum-based chemotherapy (pembrolizumab-combination) for NSCLC among patients in the phase 3 KEYNOTE-189 (ClinicalTrials.gov, NCT02578680; nonsquamous) and KEYNOTE-407 (ClinicalTrials.gov, NCT02775435; squamous) trials. Methods: This retrospective exploratory analysis evaluated prevalence of high tTMB and STK11, KEAP1, and KRAS mutations in patients enrolled in KEYNOTE-189 and KEYNOTE-407 and the relationship between these potential biomarkers and clinical outcomes. tTMB and STK11, KEAP1, and KRAS mutation status was assessed using whole-exome sequencing in patients with available tumor and matched normal DNA. The clinical utility of tTMB was assessed using a prespecified cutpoint of 175 mutations/exome. Results: Among patients with evaluable data from whole-exome sequencing for evaluation of tTMB (KEYNOTE-189, n = 293; KEYNOTE-407, n = 312) and matched normal DNA, no association was found between continuous tTMB score and overall survival (OS) or progression-free survival for pembrolizumab-combination (Wald test, one-sided p > 0.05) or placebo-combination (Wald test, two-sided p > 0.05) in patients with squamous or nonsquamous histology. Pembrolizumab-combination improved outcomes for patients with tTMB greater than or equal to 175 compared with tTMB less than 175 mutations/exome in KEYNOTE-189 (OS, hazard ratio = 0.64 [95% confidence interval (CI): 0.38-1.07] and 0.64 [95% CI: 0.42-0.97], respectively) and KEYNOTE-407 (OS, hazard ratio = 0.74 [95% CI: 0.50-1.08 and 0.86 [95% CI: 0.57-1.28], respectively) versus placebo-combination. Treatment outcomes were similar regardless of KEAP1, STK11, or KRAS mutation status. Conclusions: These findings support pembrolizumab-combination as first-line treatment in patients with metastatic NSCLC and do not suggest the utility of tTMB, STK11, KEAP1, or KRAS mutation status as a biomarker for this regimen. (c) 2022 The Authors. Published by Elsevier Inc. on behalf ofthe International Association for the Study of Lung Cancer.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | URI: | http://hdl.handle.net/10553/130505 | ISSN: | 2666-3643 | DOI: | 10.1016/j.jtocrr.2022.100431 | Fuente: | Jto Clinical And Research Reports [2666-3643],v. 4 (1), (Enero 2023) |
Colección: | Artículos |
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