Outcomes in patients with non-small cell lung cancer with brain metastases treated with pembrolizumab-based therapy

Abstract Background Patients with metastatic non-small cell lung cancer (mNSCLC) and untreated brain metastases (BM) have been excluded from most trials of immune checkpoint inhibitors (ICI). Real-world evidence on efficacy and survival outcomes of ICI in patients with BM is limited. Methods We conducted a single-center retrospective study of patients with mNSCLC treated with pembrolizumab with or without chemotherapy and compared progression-free survival (PFS) and overall survival (OS) between patients with and without BM using Kaplan-Meier and Cox methodology. We also characterized systemic and intracranial objective response rate (ORR) and treatment details, including timing of cranial irradiation. Results Between 8/2013 and 12/2018, 570 patients with mNSCLC treated with pembrolizumab-based therapy were analyzed. Of 126 (22.1%) patients with BM, 96 (76.2%) had treated BM (local therapy prior to pembrolizumab), and 30 (23.8%) had untreated BM. Of patients with untreated BM, 17 (56.7%) underwent radiation within 30 days after pembrolizumab initiation. In the remaining 13 (43.3%) treated with pembrolizumab-based therapy alone, intracranial ORR was 36.4%. Patients with and without BM did not have significantly different systemic ORR (27.8% vs 29.7%, p=0.671), PFS (mPFS 9.2 and 7.7 months, p=0.609) or OS (mOS 18.0 and 18.7 months, p=0.966). Factors associated with improved survival on Cox analysis included female sex, performance status, adenocarcinoma histology, and first-line therapy. Conclusion Patients with BM did not have inferior survival to patients without BM after treatment with pembrolizumab-based therapy. In the current era, BM may not automatically confer inferior survival, and should not exclude patients from receiving pembrolizumab-based therapy.