First-Line Treatment With Checkpoint Inhibitors in Patients With Melanoma Brain Metastases
An analysis of newly diagnosed patients with cutaneous melanoma brain metastases treated with checkpoint blockade immunotherapy has found the treatment was associated with an increase in median overall survival of 12.4 months compared with 5.2 months—a 1.4-fold improvement. The benefit was even more pronounced in patients with melanoma brain metastases without extracranial metastases: an increase in median overall survival from 7.7 months to 56.4 months and an increase in the 4-year overall survival rate from 16.9% to 51.5%. The study by Iorgulescu et al is published in Cancer Immunology Research.
Studies have shown that the incidence of melanoma continues to grow at a rate faster than any other solid tumor, with approximately 1 in 54 people expected to develop the cancer over their lifetime. Although a majority of melanomas are diagnosed at an early stage and are frequently curable, advanced melanoma usually results in a median overall survival of less than 1 year. In addition, of all the primary cancers, melanoma has one of the highest risks of metastasizing to the brain, posing significant challenges to conventional therapies.
The researchers evaluated data collected from the National Cancer Database, a hospital-based nationwide database that comprises approximately 70% of newly diagnosed cancers in the United States. They analyzed the characteristics, treatments, and overall survival of 2,753 patients with stage IV melanoma who presented with melanoma brain metastases between 2010 and 2015. The researchers further divided the patient population into those who had melanoma brain metastases–only disease (39.7%) and those who had melanoma brain metastases along with metastatic disease in another part of their body (60.3%).
Overall survival was analyzed with risk-adjusted proportional hazards and compared by Kaplan-Meier techniques.
Study Findings
The researchers found that following the U.S. Food and Drug Administration approvals of checkpoint blockade immunotherapy and BRAF V600–targeted therapy in 2011, patients with melanoma brain metastases demonstrated a 91% relative increase in 4-year overall survival to 14.1% from 7.4% preapproval (P < .001). Since approval, the proportion of patients with melanoma brain metastases who received these therapies increased from 10.5% in 2011 to 34% in 2015 (P < .001). Initial checkpoint blockade immunotherapy in patients with melanoma brain metastases displayed an improved median and 4-year overall survival of 12.4 months (compared with 5.2 months; P < .001) and 28.1% (compared with 11.1%), respectively.
These benefits were even more pronounced in patients with melanoma brain metastases without extracranial metastases, in which checkpoint blockade immunotherapy demonstrated an improved median and 4-year overall survival of 56.4 months (compared with 7.7 months; P < .001) and 51.5% (compared with 16.9%), respectively.
“Historically, most approaches to treating [central nervous system (CNS)] metastases from melanoma as well as other solid tumor types have provided minimal benefit for patients,” said David A. Reardon, MD, Clinical Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School, and a coauthor of this study. “The results of our analyses indicate that immune checkpoint inhibitors can achieve a meaningful therapeutic benefit for metastatic melanoma, including spread to the CNS. At the same time, not all patients benefit, indicating that much research is still required to optimize the potential of antitumor immune responses for CNS metastatic disease.”
J. Bryan Iorgulescu, MD, a postdoctoral fellow in the Department of Pathology at Brigham and Women’s Hospital, is the corresponding author of this study.
Funding for this study was provided by the National Institutes of Health. Disclosure of potential conflicts of interest may be found at the end of the study abstract.
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