Brain Metastases in Patients With Non-Small Cell Lung Cancer Treated With Immunotherapy. Real World Data From a Tertiary Hospital in Spain

The metastatic involvement of the central nervous system (CNS) has been traditionally related with an ominous prognosis in non-small cell lung cancer (NSCLC). Immunotherapy (IO) has (dramatically changed) revolutionized the treatment of non-oncogene addicted NSCLC but its tumour effectivity in the CNS has not been well established. The aim of this study is to identify if CNS metastases in lung cancer patients continue to be a major problem and a major cause of mortality in patients treated with IO. We performed a retrospective, observational and comparative study. We collected information regarding clinical factors, treatment, CNS involvement and outcomes from 185 patients with metastatic NSCLC treated with immunotherapy in Hospital Universitario Puerta de Hierro Majadahonda between March, 2014 and March, 2020. We performed a statistical analysis in order to exclude significant differences between both groups. We compared outcomes from patients with and without brain metastasis. 22.2% of patients had brain metastasis (CNS involvement) at diagnosis or during the course of the disease. No significant differences were found between groups regarding sex, age, histology, PD-L1, IO line, type of IO and performance status (PS). No significant differences in survival (p = 0.437) nor in the presence of long-term survivors (p = 0.723 for 2 years or more) were found. Comparative data from both groups are shown in Table-1. Specific data from patients with CNS metastases are in Table-2.Table-1Comparative dataWithout CNS metastases (N=144)With CNS metastases (N=41)PSexM: 45 (31.3%) F: 99 (68.8%)M: 19 (46.3%) F: 22 (53.7%)0.073Age (median, years; range)64.0 (40.0-82.0)58.0 (44.0-78.0)0.114HistologyAdenocarcinoma: 87 (60.4%)Squamous cell carcinoma: 42 (29.2%)Carcinoma NOS: 15 (10.4%)Adenocarcinoma: 31 (75.6%)Squamous cell carcinoma: 7 (17.1%)Carcinoma NOS: 3 (7.3%)0.199PD-L1 (median)60.055.00.638ECOG PS0-1: 134 (93.1%) 2 or more: 6 (4.1%) Unknown: 4 (2.7%)0-1: 37 (90.2%) 2 or more: 2 (4.9%) Unknown: 2 (4.9%)0.170IO line1: 41 (28.5%) 2: 50 (34.7%) Subsequent: 53 (36.8%)1: 9 (22.0%) 2: 16 (39.0%) Subsequent: 16 (9.0%)0.553Type of IOImmunotherapy: 122 (84.7%)Chemoimmunotherapy: 15 (14.9%) IO + TKI: 7 (4.9%)Immunotherapy: 35 (85.4%)Chemoimmunotherapy: 5 (12.2%) IO + TKI: 1 (2.4%)0.768Overall survival, months (median, CI 95%)Global: 16.0 (7.7-24.3) 1 line: 18.0 (7.5-28.5) 2 line: 21.0 (7.0-35.0) Subsequent lines: 8.0 (4.3-11.7)Global: 15.0 (10.3-19.7) 1 line: 19.0 (11.7-26.3) 2 line: 20.0 (0.0-43.7) Subsequent lines: 6.0 (0.1-11.9)0.437 0.860 0.342 0.706Long-term survivors2 years or more: 28 (19.4%) 3 years or more: 8 (5.6%)5 years or more: 4 (2.8%)2 years or more: 9 (22.0%) 3 years or more: 4 (9.8%)5 years or more: 2 (4.9%)0.723 0.335 0.503 Open table in a new tab Table-2Specific data from patients with brain metastasesBrain metastases before starting IO treatment20 (50.0%)Number of radiological metastases1-2: 17 (41.5%)3-10: 9 (22.0%) More than 10: 12 (29.3%) Unknown: 3 (7.30%)Meningeal carcinomatosis3 (7.5%)Local treatmentsSurgery: 3 (7.5%) Whole brain radiotherapy (WBRT): 24 (60.0%) Radiosurgery: 13 (32.5%)Radiation necrosis1 (2.5%)Best CNS responseProgressive disease: 13 (31.7%) Stable disease: 5 (12.2%) Partial response: 16 (39.0%) Complete response: 2 (4.9%) Unknown: 5 (12.2%) Open table in a new tab In our study, no significant differences were found in survival nor in the number of long-term survivors in the group of patients with brain metastases. The activity of immunotherapy on the central nervous system still needs to be defined and the impact on the outcomes of this subgroup of patients requires further investigation.