A drug already in use for several cancers was found effective in a study of leptomeningeal dissemination of cancer (LMD). LMD affects the lining of the brain and spinal cord, called the meninges. About 5-10% of patients with solid tumors eventually develop cancers in these parts of the central nervous system.

Breast cancer is the most common malignancy to metastasize to the leptomeninges. “LMD is typically deadly and patients may live only a few weeks after a diagnosis of LMD,” says Priscilla Brastianos, MD, director of the Central Nervous Metastasis Center at Massachusetts General Hospital.

In this study, the researchers tested pembrolizumab in patients with LMD from any solid malignancy. Brastianos is the lead author on the paper, which included authors from both Mass General and the Dana-Farber Cancer Institute. Their work was recently published in Nature Medicine.

More About the Study

This study included 20 patients, all women and 17 of them had breast cancer. In 70% of the patients, the original tumor had spread to other areas besides the meninges, including the lymph nodes and bone. All of the patients had received intensive treatment prior to the study: On average they had five prior systemic therapies. 

Pembrolizumab (Keytruda) is a monoclonal antibody that acts by binding to the PD-1 (programmed death-1) cell surface receptor. It is one in a class of immunotherapies that has gotten a lot of attention over the last few years because they are remarkably effective, though only in a small percent of patients. As of January 2020, pembrolizumab was FDA approved for more than a dozen solid tumors.

“LMD is becoming more common as we improve the diagnosis of this disease,” Brastianos says. “We have been looking for a treatment for a long time. Almost every clinical trial in oncology excludes patients with LMD because patients with LMD can be very sick.”

In this study, patients received 200 mg of pembrolizumab intravenously every three weeks until their disease had clearly progressed or they were experiencing unacceptable toxicity. The researchers reported that “Pembrolizumab is safe, feasible and displays promising activity in LMD patients.”

Currently LMD is treated mainly with radiation to sites where the disease is seen with imaging studies. Systemic or focused chemotherapy is also used. But management of the disease varies widely and there is no broadly accepted standard of care. In addition, radiation to the brain and spinal cord can have serious side effects.

“It’s good to know that there is a promising option,” says Brastianos.

Paper cited: Brastianos PK, Lee EQ, Cohen JV, et al. Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis [published online ahead of print, 2020 Jun 1]. Nat Med. 2020;10.1038/s41591-020-0918-0.

Funding: Funding was provided by the Melanoma Research Alliance, the Breast Cancer Research Foundation, Merck and the Massachusetts General Hospital. P.K.B. and S.L.C. are supported by the National Cancer Institute (1R01CA227156-01, 5R21CA220253-02 and 1R01CA244975-01). P.K.B. is also currently supported by the Damon Runyon Cancer Research Foundation and has previously received funding from the Susan G. Komen Foundation, the American Brain Tumor Association, the Terri Brodeur Breast Cancer Foundation and the Conquer Cancer Foundation. 

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of over $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2019, the Mass General was named #2 in the U.S. News & World Report list of "America’s Best Hospitals."