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

Autor: Lauko A; Case Western Reserve University School of Medicine MSTP, Cleveland, OH, USA., Kotecha R; Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.; Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA., Barnett A; Rosa Ella Burkhart Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland, OH, USA., Li H; Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Tatineni V; Department of Internal Medicine, Summa Health, Akron City Hospital, Akron, OH, USA., Ali A; Rosa Ella Burkhart Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland, OH, USA., Patil P; Department of Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA., Mohammadi AM; Case Western Reserve University School of Medicine MSTP, Cleveland, OH, USA.; Rosa Ella Burkhart Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland, OH, USA.; Department of Neurological Surgery, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA., Chao ST; Rosa Ella Burkhart Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland, OH, USA.; Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA., Murphy ES; Rosa Ella Burkhart Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland, OH, USA.; Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA., Angelov L; Case Western Reserve University School of Medicine MSTP, Cleveland, OH, USA.; Rosa Ella Burkhart Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland, OH, USA.; Department of Neurological Surgery, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA., Suh JH; Rosa Ella Burkhart Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland, OH, USA.; Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA., Barnett GH; Case Western Reserve University School of Medicine MSTP, Cleveland, OH, USA.; Rosa Ella Burkhart Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland, OH, USA.; Department of Neurological Surgery, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA., Pennell NA; Department of Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA., Ahluwalia MS; Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA. manmeeta@baptisthealth.net.; Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, 8900 North Kendall Drive, Miami, FL, 33176, USA. manmeeta@baptisthealth.net.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Sep 13; Vol. 11 (1), pp. 18174. Date of Electronic Publication: 2021 Sep 13.
DOI: 10.1038/s41598-021-97566-z
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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