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Newswise — New Haven, Conn. — Lung cancer spreads to the brain in about one-quarter of patients with an advanced form of the disease. To date, radiation has been the only treatment option, despite the significant toxicity often linked to the treatment. Researchers at Yale Cancer Center (YCC) have found that use of the checkpoint inhibitor pembrolizumab can extend life with very few side effects in this patient population.
The findings, published online in the journal The Lancet Oncology, found that patient response depended on the level of biomarker (PD-L1) the tumor expressed. But of those that did respond, overall survival at one year was 40% and 34% at two years.
“Survival in this cohort of patients exceeds the historically documented survival for patients with brain metastasis from non-small cell lung cancer or NSCLC, which is a 2-year survival of about 14%,” said the study’s lead investigator Sarah B. Goldberg, M.D., M.P.H., associate professor of Medicine (Medical Oncology) at YCC.
This is the first study to specifically test benefit of the treatment in a prospective clinical trial of lung cancer patients who had not yet been treated for brain metastasis or whose tumors recurred after radiation. Before this, most clinical trials of a checkpoint immunotherapy drug did not include patients with brain metastasis, but the few that did provided hints of benefit, when retrospectively analyzed.
“We have clearly shown, for the first time, that brain metastasis responds to a targeted immunotherapy treatment for lung cancer,” Goldberg said. “In general, we found that the benefit offered by pembrolizumab to the lungs in patients with advanced lung cancer was mirrored in control of their brain tumors. The brain and body response were the same.”
This phase 2, single institution, open label study enrolled 42 patients with small brain tumors (5-20 mm) that had not been previously treated or which progressed after radiation treatment.
Patients did not have neurologic symptoms. “We did not enroll patients with larger tumors or neurologic issues because, as the first study of this protocol, we did not know if there would be side effects and we did not want to cause harm,” said Goldberg. “As it turns out, we found the drug was safe, and the neurologic adverse events were very few and unrelated to the drug.”
Patients were divided into two groups: patients in cohort 1 that had some PD-L1 activity and those, in cohort 2, that had none. Researchers found that none of the six patients in cohort 2 responded to pembrolizumab.
Goldberg theorizes that patients in cohort 1 that had a good, long lasting response likely had brain tumors that have more PD-L1 expression than those that didn’t experience a longer lasting benefit. “But we don’t know that yet. This idea needs to be tested.”
Goldberg added, with further study and biomarker analysis, “it might make sense for some patients to try a checkpoint inhibitor first to treat both their lung cancer and brain metastasis. Radiation could follow, if necessary.” But she added that such a change would take time to become a tool in the NSCLC brain metastasis medical kit. “The standard of care is radiation, and sometimes, whole brain radiation. Further investigation of this therapy is needed.”
Funding for the research was provided by Merck and YCC.
About Yale Cancer Center and Smilow Cancer Hospital Yale Cancer Center (YCC) is one of only 51 National Cancer Institute (NCI-designated comprehensive cancer) centers in the nation and the only such center in Connecticut. Cancer treatment for patients is available at Smilow Cancer Hospital through 13 multidisciplinary teams and at 15 Smilow Cancer Hospital Care Centers in Connecticut and Rhode Island. Smilow Cancer Hospital is accredited by the Commission on Cancer, a Quality program of the American College of Surgeons. Comprehensive cancer centers play a vital role in the advancement of the NCI’s goal of reducing morbidity and mortality from cancer through scientific research, cancer prevention, and innovative cancer treatment.
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