Real world outcomes of combination and timing of immunotherapy with radiotherapy for melanoma with brain metastases

Abstract

Introduction: Immunotherapy (IT) and radiotherapy (RT) have improved overall survival in patients with melanoma with brain metastasis (MBM). We examined the real-world survival impact of IT and RT combination and timing strategies.

Materials and methods: From the facility-based National Cancer Database (NCDB) data set, 3008 cases of MBM were identified between 2011 and 2015. Six treatment cohorts were identified: stereotactic radiosurgery (SRS) + IT, SRS alone, whole brain radiotherapy (WBRT) + IT, WBRT alone, IT alone, and none. Concurrent therapy was defined as IT given within 28 days before or after RT; nonconcurrent defined as IT administered within 28-90 days of RT. The co-primary outcomes were propensity score-adjusted overall survival by treatment regimen and overall survival by RT and IT timing.

Results: Median overall survival (mOS) was performed for each treatment category; SRS +IT 15.77 m; (95%CI 12.13-21.29), SRS alone (9.33 m; 95%CI: 8.0-11.3), IT alone (7.29 m; 95%CI: 5.35-12.91), WBRT +IT (4.89 m; 95%CI: 3.65-5.92), No RT or IT (3.29 m; 95%CI: 2.96-3.75), and WBRT alone (3.12 m; 95%CI 2.79-3.52). By propensity score matching, mOS for SRS +IT (15.5 m; 95%CI: 11.5-20.2) was greater than SRS alone (10.1 m; 95%CI: 8.4-11.8) (p = 0.010), and median survival for WBRT +IT (4.6 m; 95%CI: 3.4-5.6) was greater than WBRT alone (2.9 m; 95%CI: 2.5-3.5) (p < 0.001). In the SRS +IT group, 24-month landmark survival was 47% (95%CI; 42-52) for concurrent versus 37% (95%CI; 30-44) for nonconcurrent (p = 0.40).

Conclusion: Those who received IT in addition to WBRT and SRS experienced longer survival compared to RT modalities alone, while those receiving concurrent SRS and IT trended toward improved survival versus nonconcurrent therapy.

Keywords: NCDB; brain metastasis; immunotherapy; melanoma; stereotactic radiosurgery; whole brain radiotherapy.

FIGURE 1

CONSORT diagram of case allocation

FIGURE 2

(A) Percentage of patients receiving each treatment by year. IT, Immunotherapy, SRS, Stereotactic radiosurgery, WBRT, whole brain radiotherapy. (B) Overall Survival by treatment regimen. IT, Immunotherapy, SRS, Stereotactic radiosurgery, WBRT, whole brain radiotherapy. (C) Propensity score matched overall survival by SRS +IT versus SRS. (D) Propensity score matched overall survival by WBRT +IT versus SRS

FIGURE 3

Cox Regression for survival. HR less than 1 show benefit for increased survival, whereas HR greater than 1 are increased hazard for death. HR, Hazard ratio; IT, Immunotherapy; SRS, Stereotactic radiosurgery; WBRT, whole brain radiotherapy

FIGURE 4

(A) First day of immunotherapy prior to first day of radiation (as negative values) or after the last day of radiation (as positive values). First day of immunotherapy given during course of radiation is listed as day 0. (B) Concurrent (CC) versus Non‐Concurrent (NCC) combination immunotherapy and radiation for SRS +IT. (C) Concurrent (CC) versus Non‐Concurrent (NCC) combination immunotherapy and radiation for WBRT + IT