PHILADELPHIA — Among patients with cutaneous melanoma who had brain metastases (MBM), first-line treatment with a checkpoint inhibitor was associated with a 1.4-fold increase in median overall survival, according to results from a national cohort published in Cancer Immunology Research, a journal of the American Association for Cancer Research.
“Checkpoint blockade immunotherapies have revolutionized how we care for patients with advanced melanoma, leading to long-lasting treatment responses in many patients,” said J. Bryan Iorgulescu, MD, postdoctoral fellow in the Department of Pathology at Brigham and Women’s Hospital/Harvard Medical School and Department of Medical Oncology at the Dana-Farber Cancer Institute. “However, many of the early clinical trials of checkpoint blockade immunotherapies included few melanoma patients with brain metastases – despite their high incidence – and so the survival benefits of these exciting therapies remained unclear for this substantial subset of patients.”
Iorgulescu and colleagues evaluated data collected from the National Cancer Database (NCDB), which includes information for approximately 70 percent of newly diagnosed patients with cancer in the United States. They analyzed the characteristics, treatments, and overall survival of 2,753 stage 4 melanoma patients who presented with MBMs between 2010 and 2015. The population was further divided into those who had MBM-only disease (patients with brain metastases but no metastases in any other part of the body; 39.7 percent of patients) and those who had MBM with metastatic disease detected in another part of the body (60.3 percent of patients).
Overall, following the U.S. Food and Drug Administration (FDA) approvals of checkpoint blockade immunotherapies, the percentage of patients with MBMs that received these therapies increased from 10.5 percent in 2011 to 34 percent in 2015. Following multivariable analysis, the researchers found that first-line treatment of MBM patients with checkpoint blockade immunotherapy was associated with an increase in median overall survival from 5.2 months to 12.4 months, corresponding to a 1.4-fold improvement. Furthermore, the treatment was associated with an increase in the four-year overall survival rate for this group of patients from 11.1 percent to 28.1 percent, corresponding to a 1.5-fold improvement.
MBM-only patients had more pronounced results; first-line treatment with checkpoint blockade immunotherapy was associated with an increase in the median overall survival from 7.7 months to 56.4 months and an increase in the four-year overall survival rate from 16.9 percent to 51.5 percent.
Iorgulescu and colleagues also found that MBM patients were more likely to receive checkpoint blockade immunotherapy if they were younger, had fewer comorbidities, or were insured privately or through Medicare (versus uninsured), among other reasons.
“Historically, most approaches to treating CNS [central nervous system] 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 the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School and mentor to Iorgulescu. “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 anti-tumor immune responses for CNS metastatic disease.”
“Through the use of nationwide cancer data, for the first time we can evaluate the impacts on survival that these exciting new therapies have for patients with melanoma brain metastases, highlighting the power of population data to help answer critical, but previously unanswerable, questions that we face every day in clinical practice," said senior author Timothy Smith, MD, PhD, MPH, director of the Computational Neuroscience Outcomes Center at the Department of Neurosurgery at Brigham and Women’s Hospital/Harvard Medical School.
Iorgulescu explained that limitations of the NCDB include a lack of data beyond patients’ initial diagnosis. Thus, the results reported here may not apply to the majority of MBMs that develop following initial presentation. He also noted that the NCDB lacks detailed information about specific immunotherapeutic agents, and while biochemotherapeutics would be also be encoded as immunotherapy, the majority of NCDB-coded immunotherapy following FDA approval in 2011 should represent checkpoint blockade immunotherapy in this study.
Iorgulescu is supported by the National Institutes of Health. Iorgulescu declares no conflict of interest.