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

• Published in: Scientific reports Vol. 11; no. 1; p. 18174
• Main Authors: Lauko, Adam, Kotecha, Rupesh, Barnett, Addison, Li, Hong, Tatineni, Vineeth, Ali, Assad, Patil, Pradnya, Mohammadi, Alireza M., Chao, Samuel T., Murphy, Erin S., Angelov, Lilyana, Suh, John H., Barnett, Gene H., Pennell, Nathan A., Ahluwalia, Manmeet S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-09-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4028/67/1612/1350; 692/4028/67/1922; Aged; Brain cancer; Brain Neoplasms - secondary; Brain Neoplasms - therapy; Clinical trials; Female; Humanities and Social Sciences; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; K-Ras protein; Lung cancer; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Male; Medical prognosis; Metastases; Metastasis; Middle Aged; multidisciplinary; Multivariate Analysis; Mutation; Mutation - genetics; Non-small cell lung carcinoma; Patients; PD-L1 protein; Proto-Oncogene Proteins p21(ras) - genetics; Radiosurgery; Science; Science (multidisciplinary); Small cell lung carcinoma
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-97566-z

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.