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

Abstract

Immune checkpoint inhibitors (ICI) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have shown responses in the management of non-small cell lung cancer (NSCLC) brain metastases (BM). However, optimizing control with stereotactic radiosurgery (SRS) and various systemic therapies in the management of NSCLC BM remains an area of investigation. We evaluated clinical outcomes in NSCLC BM treated with SRS and ICI, EGFR-TKI, ICI and chemotherapy, compared to conventional chemotherapy.A total of 174 NSCLC BM patients, treated between 2015 and 2019, to a total of 660 intact (non-operative) BM over 239 single-fraction SRS sessions within 3 months of receiving ICI (n = 58; 33%), EGFR-TKI (n = 30; 17%), chemotherapy and ICI (n = 22; 13%) or standard chemotherapy (n = 64; 37%) were identified. Time-to-event analysis was conducted with the Kaplan-Meier method, and outcomes included distant intracranial control (DIC), local control (LC), and overall survival (OS) from SRS. Cox proportional hazards model was utilized for multivariate analysis (MVA) to identify correlations of clinical variables with outcomes.Median follow-up from BM diagnosis was 8.9 months (0.26-126.5 months) and 7.3 months from SRS (2.5-17.6 months). No significant differences in age (P = 0.55), gender (P = 0.49), treated gross tumor volume (P = 0.31), presence of systemic metastasis (P = 0.1), SRS dose (P = 0.61), or KPS (0.35) were noted between treatment groups. The 12-month DIC was 35%, 53%, 41%, and 20% (P = 0.02) for ICI, EGFR-TKI, ICI and chemotherapy, and chemotherapy alone groups, respectively. No differences were noted in LC (P = 0.1) and OS (P = 0.5) between treatment groups. Upon MVA, factors found to be significant for improved DIC included treatment with EGFR-TKI therapy compared to conventional chemotherapy (HR 0.4; 95% CI 0.25-0.76; P = 0.04) and treatment with SRS before systemic therapy (HR 0.6; 95% CI 0.3-0.9; P = 0.03). Factors found to be significant for improved LC on MVA included treatment with SRS before (HR 0.4; 95% CI 0.2-0.9; P = 0.03) or concurrent (HR 0.3; 95% CI 0.1-0.6; P = 0.003) compared to following receipt of systemic therapy. Rates of radiation necrosis (RN) did not differ between treatment groups and were 6% (n = 12), 5% (n = 12), 3% (n = 3), 3% (n = 3), for ICI, EGFR-TKI, ICI and chemotherapy, and chemotherapy alone groups, respectively, P = 0.43. In addition, no differences were noted in RN between timing of SRS and receipt of systemic therapy, (P = 0.81).In our analysis of NSCLC BM patients treated with single session SRS alongside systemic therapy, we found significant differences in DIC based on receipt of systemic therapy. In addition, treatment with SRS before or concurrent with systemic therapy improved control rates. No differences in RN were noted between treatment groups or by timing of SRS and systemic therapy. Prospective evaluation of the potential synergistic effect between systemic therapy and SRS in NSCLC BM management is warranted.A.E. Dohm: None. J. Tang: None. M.N. Mills: None. B.A. Perez: Research Grant; BMS.T.J. Robinson: None. B. Creelan: Research Grant; NGenomics Laboratories, Adaptive Biotechnologies Corp. Consultant; Xilio Inc, E.R. Squibb LLC, F. Hoffmann-La Roche AG, AstraZeneca plc, AbbVie, KSQ Therapeutics Inc, GlaxoSmithKline plc, Gilead Sciences Inc, Celgene corp. Speaker's Bureau; AstraZeneca plc, ARIAD Pharmaceuticals, Hoffmann-La Roche AG.J. Gray: None. A.B. Etame: None. M. Vogelbaum: Honoraria; Celgene, Tocagen. Stock Options; Infuseon Therapeutics. Royalty; Infuseon Therapeutics. P. Forsyth: Research Grant; Pfizer, Celgene. Advisory Board; Novocure, BTG, Inovio, AbbVie, Ziopharm, Tocagen, Pfizer. H.M. Yu: Honoraria; UpToDate. Speaker's Bureau; BrainLab. Advisory Board; Novocure, AbbVie. D.E. Oliver: None. K.A. Ahmed: Research Grant; Bristol-Myers Squibb, Genentech.