Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases

Abstract Immune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICI...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Adam Lauko, Rupesh Kotecha, Addison Barnett, Hong Li, Vineeth Tatineni, Assad Ali, Pradnya Patil, Alireza M. Mohammadi, Samuel T. Chao, Erin S. Murphy, Lilyana Angelov, John H. Suh, Gene H. Barnett, Nathan A. Pennell, Manmeet S. Ahluwalia
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e1027f0afb7f466d803752a48a7d5614
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e1027f0afb7f466d803752a48a7d5614
record_format	dspace
spelling	oai:doaj.org-article:e1027f0afb7f466d803752a48a7d56142021-12-02T15:33:23ZImpact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases10.1038/s41598-021-97566-z2045-2322https://doaj.org/article/e1027f0afb7f466d803752a48a7d56142021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97566-zhttps://doaj.org/toc/2045-2322Abstract Immune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICIs within 90 days of NSCLCBM diagnosis (ICI-90) and compared them to patients who never received ICIs (no-ICI). We reviewed 800 patients with LCBM who were diagnosed between 2010 and 2019 at a major tertiary care institution, 97% of whom received stereotactic radiosurgery (SRS) for local treatment of BM. OS from BM was compared between the ICI-90 and no-ICI groups using the Log-Rank test and Cox proportional-hazards model. Additionally, the impact of KRAS mutational status on the efficacy of ICI was investigated. After accounting for known prognostic factors, ICI-90 in addition to SRS led to significantly improved OS compared to no-ICI (12.5 months vs 9.1, p < 0.001). In the 109 patients who had both a known PD-L1 expression and KRAS status, 80.4% of patients with KRAS mutation had PD-L1 expression vs 61.9% in wild-type KRAS patients (p = 0.04). In patients without a KRAS mutation, there was no difference in OS between the ICI-90 vs no-ICI cohort with a one-year survival of 60.2% vs 54.8% (p = 0.84). However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients. Additionally, this benefit appears to be observed primarily in patients with KRAS mutations that may drive the overall benefit, which should be taken into account in the development of future trials.Adam LaukoRupesh KotechaAddison BarnettHong LiVineeth TatineniAssad AliPradnya PatilAlireza M. MohammadiSamuel T. ChaoErin S. MurphyLilyana AngelovJohn H. SuhGene H. BarnettNathan A. PennellManmeet S. AhluwaliaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adam Lauko Rupesh Kotecha Addison Barnett Hong Li Vineeth Tatineni Assad Ali Pradnya Patil Alireza M. Mohammadi Samuel T. Chao Erin S. Murphy Lilyana Angelov John H. Suh Gene H. Barnett Nathan A. Pennell Manmeet S. Ahluwalia Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases
description	Abstract Immune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICIs within 90 days of NSCLCBM diagnosis (ICI-90) and compared them to patients who never received ICIs (no-ICI). We reviewed 800 patients with LCBM who were diagnosed between 2010 and 2019 at a major tertiary care institution, 97% of whom received stereotactic radiosurgery (SRS) for local treatment of BM. OS from BM was compared between the ICI-90 and no-ICI groups using the Log-Rank test and Cox proportional-hazards model. Additionally, the impact of KRAS mutational status on the efficacy of ICI was investigated. After accounting for known prognostic factors, ICI-90 in addition to SRS led to significantly improved OS compared to no-ICI (12.5 months vs 9.1, p < 0.001). In the 109 patients who had both a known PD-L1 expression and KRAS status, 80.4% of patients with KRAS mutation had PD-L1 expression vs 61.9% in wild-type KRAS patients (p = 0.04). In patients without a KRAS mutation, there was no difference in OS between the ICI-90 vs no-ICI cohort with a one-year survival of 60.2% vs 54.8% (p = 0.84). However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients. Additionally, this benefit appears to be observed primarily in patients with KRAS mutations that may drive the overall benefit, which should be taken into account in the development of future trials.
format	article
author	Adam Lauko Rupesh Kotecha Addison Barnett Hong Li Vineeth Tatineni Assad Ali Pradnya Patil Alireza M. Mohammadi Samuel T. Chao Erin S. Murphy Lilyana Angelov John H. Suh Gene H. Barnett Nathan A. Pennell Manmeet S. Ahluwalia
author_facet	Adam Lauko Rupesh Kotecha Addison Barnett Hong Li Vineeth Tatineni Assad Ali Pradnya Patil Alireza M. Mohammadi Samuel T. Chao Erin S. Murphy Lilyana Angelov John H. Suh Gene H. Barnett Nathan A. Pennell Manmeet S. Ahluwalia
author_sort	Adam Lauko
title	Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases
title_short	Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases
title_full	Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases
title_fullStr	Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases
title_full_unstemmed	Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases
title_sort	impact of kras mutation status on the efficacy of immunotherapy in lung cancer brain metastases
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e1027f0afb7f466d803752a48a7d5614
work_keys_str_mv	AT adamlauko impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT rupeshkotecha impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT addisonbarnett impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT hongli impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT vineethtatineni impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT assadali impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT pradnyapatil impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT alirezammohammadi impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT samueltchao impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT erinsmurphy impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT lilyanaangelov impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT johnhsuh impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT genehbarnett impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT nathanapennell impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases AT manmeetsahluwalia impactofkrasmutationstatusontheefficacyofimmunotherapyinlungcancerbrainmetastases
_version_	1718387114876338176

Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases

Ejemplares similares