Outcome of Patients with NSCLC and Brain Metastases Treated with Immune Checkpoint Inhibitors in a ‘Real-Life’ Setting

SIMPLE SUMMARY: We identified non-small cell lung cancer (NSCLC) patients with brain metastases who were treated with immune checkpoint inhibitors at Karolinska University Hospital, Sweden and University Hospital of Heraklion, Greece from 2016 to 2019. We analyzed intracranial efficacies in the patients who had not received local treatment for their brain metastases less than three months prior to the initiation of immune checkpoint inhibitors and had adequate radiological evaluation. We demonstrated that immune checkpoint inhibitors are active in NSCLC patients with brain metastases regardless of the presence of neurological symptoms. This is a novel finding since, until now, this patient group has irrefutably been underrepresented in clinical studies and there is a clear scarcity of data. The results of our analyses suggest that symptomatic patients with active brain metastases (BM) may be considered for immunotherapy in routine clinical practice as well as clinical trials. ABSTRACT: There is lack of data addressing the intracranial (IC) efficacy of immune checkpoint inhibitors (ICIs) on brain metastases (BM) in non-small cell lung cancer (NSCLC). This patient category is underrepresented in randomized clinical trials. We retrospectively collected clinical data on patients with non-oncogenic driven NSCLC with BM who were treated with ICIs at two medical oncology institutes in Sweden and Greece from 2016 to 2019. IC efficacy was assessed in patients who had not received local treatment for BM less than three months prior to the initiation of ICIs and had adequate radiological evaluation. We screened 280 patients, of which 51 had BM. BM was an independent predictor for inferior PFS (HR = 2.27; 95% CI, 1.53–3.36) but not OS (HR = 1.58; 95% CI, 0.97–2.60) for the whole patient population. IC response assessment was done on 33 patients. IC objective response rate (ORR) was 24.2%. The presence of neurological symptoms related to BM did not affect IC ORR (p = 0.48). High PD-L1 levels from extracranial biopsies were not a predictive factor for IC ORR (p = 0.13). ICIs are active in NSCLC patients with BM regardless of the presence of neurological symptoms and can achieve durable IC disease stabilization in a subgroup of patients.