Clinical outcomes of non-small cell lung cancer brain metastases treated with stereotactic radiosurgery and immune checkpoint inhibitors, EGFR tyrosine kinase inhibitors, chemotherapy and immune checkpoint inhibitors, or chemotherapy alone

OBJECTIVE Immune checkpoint inhibitors (ICIs) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are commonly used in the systemic management of non-small cell lung cancer (NSCLC) brain metastases (BMs). However, optimizing control of NSCLC BM with stereotactic radiosurgery (SRS) and various systemic therapies remains an area of investigation. METHODS Between 2016 and 2019, the authors identified 171 NSCLC BM patients with 646 BMs treated with singlefraction SRS within 3 months of receiving treatment with ICIs (n = 56; 33%), EGFR-TKI (n = 30; 18%), chemotherapy and ICIs (n = 23; 14%), or standard chemotherapy alone (n = 62; 36%). Time-to-event analysis was conducted, and outcomes included distant intracranial control (DIC), local control (LC), and overall survival from SRS. RESULTS The median follow-up from BM diagnosis was 8.9 months (range 0.3-127 months). The 12-month KaplanMeier DIC rates were 37%, 53%, 41%, and 21% (p = 0.047) for the ICI, EGFR-TKI, ICI and chemotherapy, and chemotherapy-alone groups, respectively. On multivariate analysis, DIC was improved with EGFR-TKI (HR 0.4, 95% CI 0.3-0.8, p = 0.005) compared with conventional chemotherapy and treatment with SRS before systemic therapy (HR 0.5, 95% CI 0.3-0.9, p = 0.03) compared with after; and LC was improved with SRS before (HR 0.4, 95% CI 0.2-0.9, p = 0.03) or concurrently (HR 0.3, 95% CI 0.1-0.6, p = 0.003) compared with after. No differences in radionecrosis were noted by timing or type of systemic therapy. CONCLUSIONS The authors' analysis showed significant differences in DIC based on receipt of systemic therapy and treatment with SRS before systemic therapy improved DIC. Prospective evaluation of the potential synergism between systemic therapy and SRS in NSCLC BM management is warranted.