Improved Risk-Adjusted Survival for Melanoma Brain Metastases in the Era of Checkpoint Blockade Immunotherapies: Results from a National Cohort

Abstract

The successes of checkpoint blockade immunotherapy (CBI) and BRAF-targeted therapy trials have generated substantial promise for revolutionizing the management of patients with advanced melanoma. However, because early clinical trials of CBIs and BRAF-targeted therapy either excluded or included disproportionately fewer cases of melanoma brain metastases (MBMs), the survival benefit of these novel therapies for MBM remains unknown. We, therefore, evaluated the characteristics, management, and overall survival (OS) of patients who presented with cutaneous MBMs during 2010 to 2015 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. We found that 2,753 (36%) of patients presenting with stage 4 melanoma had MBMs. Following the 2011 FDA approvals for CBI and BRAF-targeted therapy, MBM patients demonstrated a 91% relative increase in 4-year OS to 14.1% from 7.4% preapproval ( < 0.001). Postapproval, the proportion of MBM patients who received CBI rose from 10.5% in 2011 to 34.0% in 2015 ( < 0.001). Initial CBI in MBM patients displayed an improved median and 4-year OS of 12.4 months (compared with 5.2 months; < 0.001) and 28.1% (compared with 11.1%), respectively. These benefits were pronounced in MBM patients without extracranial metastases, in which CBI demonstrated improved median and 4-year OS of 56.4 months (compared with 7.7 months; < 0.001) and 51.5% (compared with 16.9%), respectively. Using a large national cohort composed of a "real-life" MBM treatment population, we demonstrated the dramatic OS improvements associated with novel checkpoint blockade immunotherapies. .

Immunotherapy in sinonasal melanoma: treatment patterns and outcomes compared to cutaneous melanoma

“…Other investigations evaluating the role of immunotherapy using NCDB data have used similar date-based cutoffs to infer specific therapeutics used as standard-of-care for given diseases, or have assumed that immunotherapy consisted of checkpoint inhibitors. 42,[44][45][46] The only other NCDB study evaluating immunotherapy in SNM examined patients diagnosed from 2004 to 2015, without stratification based on time period or regard for changes in the definition of "immunotherapy." 42 Such an approach is unlikely to elucidate the role of checkpoint inhibition in this disease, as prior to 2011 the vast majority of immunotherapy likely consisted of other targeted agents.…”

Autoimmunity in Acute Myocarditis: How Immunopathogenesis Steers New Directions for Diagnosis and Treatment

“…Combination of ICI treatment increases the risk of myocarditis as compared with single drug therapy. Given the early success of ICI in advanced cancer [17], we expect to see an increase of autoimmune diseases related to this novel drug class in the future [18].…”

Integration of stereotactic radiosurgery or whole brain radiation therapy with immunotherapy for treatment of brain metastases

“…Among them, the largest study was conducted by Iorgulescu et al . They conducted analysis on data, from the National Cancer Database, of 220,439 patients diagnosed with melanoma from 2010 to 2015, and found that in comparison to OS of 5.2 months for patients not treated with ICIs, immunotherapy lengthened OS to 12.4 months ( 10 ). In contrast, the number of prospective clinical trials in this field is small.…”

“…Therefore, evidence regarding the use of ICIs in treating patients with BM is limited, and many questions remain unresolved. In some clinical studies, findings have suggested that ICIs are effective in enhancing the OS of patients with BM ( 10 , 11 ). However, the results have not been confirmed by a large prospective phase III clinical study.…”