Abstract
BACKGROUND
The recent successes of checkpoint blockade immunotherapy (CBI) and BRAFV600-targeted therapy trials have generated substantial promise for revolutionizing the management of patients with advanced melanoma. However, because early clinical trials of CBIs and BRAFV600-targeted therapy either excluded or included disproportionately fewer cases of melanoma brain metastases (MBM), the survival benefit of these novel therapies for MBM remains unknown.
METHODS
The characteristics, management, and overall survival (OS) of patients who presented with cutaneous MBMs during 2010–2015 were evaluated using the National Cancer Database, which comprises 70% of all newly diagnosed U.S. cancers. OS was analyzed with risk-adjusted proportional hazards and compared by Kaplan-Meier techniques.
RESULTS
2,753 (36%) of patients presenting with stage 4 melanoma had MBMs. Following the 2011 FDA approvals for CBI and BRAFV600-targeted therapy, MBM patients demonstrated a 91% relative increase in 4-yr OS to 14.1% (95CI:12.2–16.1) from 7.4% pre-approval (95CI:5.3–10.0, p<0.001). Post-approval, the proportion of MBM patients that received CBI rose from 10.5% in 2011 to 34.0% in 2015 (p<0.001). MBM patients were more likely to receive CBI if they were younger, more recently diagnosed, had fewer comorbidities, insured privately or through Medicare, diagnosed in New England, had brain-directed RT, or had involvement of other metastatic sites. Initial CBI in MBM patients displayed a 2.4x improved median and 4-yr OS of 12.4 mos (95CI:10.4–15.8; vs. 5.2 mos, 95CI:4.7–5.9, p<0.001) and 28.1% (95CI:22.1–34.4; vs. 11.1%, 95CI:9.3–13.1), which persisted in multivariable analyses (HR 0.12, 95CI:0.03–0.49, p=0.003). These benefits were pronounced in MBM patients without extracranial metastases, in which CBI demonstrated improved median and 4-yr OS of 56.4 mos (95CI:25.0-NR; vs. 7.7 mos, 95CI:6.7–8.7, p<0.001) and 51.5% (95CI:38.9–62.8; vs. 16.9%, 95CI:13.5–20.6).
CONCLUSION
Using a large national cohort composed of a “real-life” MBM treatment population, we demonstrate the dramatic OS improvements associated with novel checkpoint blockade immunotherapies.