TITLE:
Predictive Factors of Intracranial Response of Immune Checkpoint Inhibitors in Patients with Brain Metastasis from Non-Small Cell Lung Cancer
AUTHORS:
Julien Bermudez, Celine Mascaux, Youssef Trigui, Julie Biemar, Mohamed Boucekine, Laurent Greillier, Fabrice Barlesi, Pascale Tomasini
KEYWORDS:
Lung Cancer, Brain Metastasis, Immunotherapy, Efficacy, Tolerance
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.10 No.8,
August
28,
2019
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.