Abstract
Background: Immune checkpoint inhibitors (ICI)s were recently approved for the treatment of advanced non-small cell lung cancer (NSCLC). Whereas brain metastases (BM) are frequent in NSCLC patients, data are missing regarding ICIs intracranial efficacy and tolerance in patients with BM from NSCLC. Methods: This retrospective study was performed in the Multidisciplinary Oncology and Therapeutic Innovation department, Marseille, France between April 2013 and February 2016. Data from patients with NSCLC with at least one BM, and treated with ICIs (anti-PD1, anti-PDL1 or anti-CTL4) were analyzed. Clinical, biological data and outcomes were retrieved from electronic patients’ records. We assessed ICIs intracranial efficacy and tolerance. Results: Data from 55 patients were analyzed. Objective Response Rate (ORR) and Disease Control Rate (DCR) were respectively of 1.8 and 36.4%. Median overall survival was 17.2 months and median progression free survival was 2.9 months. Intracranial ORR (icORR) and intracranial DCR (icDCR) were respectively 16.4% and 45.5%. Both were independent of smoking status, intracranial treatment, performance status, pathology, molecular profile and the presence or number of BM at diagnosis. However, there was a trend towards an association between icORR and ECOG PS (p = 0.05), tobacco status (p = 0.057) and intracranial treatment. Adverse events were seen in 38.2% patients without identified predictive factor. Neurological symptoms appeared in 5.5% patients during immunotherapy and improved in 3.63% patients. Conclusions: ICIs can be used safely on patients with BM from NSCLC. However, intracranial response is heterogeneous in such patients and we showed ECOG PS, tobacco smoking and intracranial treatment to be associated with an improved icORR. This is the first study looking for predictive factors of intracranial response of ICIs in patients with BM from NSCLC.
Highlights
IntroductionLung cancer is the leading cause of brain metastases (BM): 40% to 50% of BMs come from lung cancers [1] and in autopsy series, up to 50% of patients with lung cancer were found with BM [2]
Our study is the first and largest series reporting factors associated with favorable outcomes in patients with brain metastases (BM) from non-small cell lung cancer (NSCLC) treated with Immune checkpoint inhibitors (ICI)
In a population of 55 patients, we have shown that intracranial disease control was achieved in nearly half patients, regardless of local brain treatments received previously
Summary
Lung cancer is the leading cause of brain metastases (BM): 40% to 50% of BMs come from lung cancers [1] and in autopsy series, up to 50% of patients with lung cancer were found with BM [2]. BMs are discovered at the time of diagnosis in 10% of patients with non-small cell lung cancer (NSCLC) [3]. They are known to be associated with a poor prognosis and are the immediate cause of death in 50% of patients with solid tumors [4]. The addition of bevacizumab to standard first- or second-line chemotherapy increased overall survival (OS) of patients with NSCLC BM up to 16 months in a phase II study [9]. Intracranial ORR (icORR) and intracranial DCR (icDCR) were respectively 16.4% and 45.5% Both were independent of smoking status, intracranial treatment, performance status, pathology, molecular profile and the presence or number of BM at diagnosis. Neurological symptoms appeared in 5.5% patients during immunotherapy and improved in 3.63% pa-
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