In a study funded by Yale Cancer Center and Merck, investigators learned that in about 25% of patients with an advanced form of lung cancer, it spreads to the brain. Thus far, the only way to combat such a situation is with radiation. However, consequences of such treatment includes toxic side effects. Investigators recently found that the use of pembrolizumab (Keytruda), a Merck checkpoint inhibitor, in place of radiation can extend life with less side effects in this patient segment.
The study findings were published by Yale in the April 13 edition of The Lancet Oncology. The investigators found that patient response was influenced by the level of the biomarker (PD-L1) expressed in individual tumors. Of those that did respond, survival at one year was 40% and 34% at team years.
This Yale Cancer Center-led study is a first—the first one to specifically test the 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. Prior to this study, most clinical trial studies involving a checkpoint immunotherapy treatment precluded patients with brain metastasis; however, Yale Cancer Center reports that the few that did so offered hints of benefit based on retrospective analyses.
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 that 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 principal investigator Sarah B. Goldberg, MD, MPH. “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 had some PD-L1 activity; those in cohort 2 had none. Researchers found that none of the six patients in cohort 2 responded to pembrolizumab.
“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.”
Yale Cancer Center
Founded in 1974, Yale Cancer Center was created as an act of Congress in 1971 as part of the declaration of the “War on Cancer.” It is one of a network of 51 Comprehensive Cancer Centers designated by the Cancer Institute. The center offers some factoids:
• Celebrating 45 years as Connecticut’s only comprehensive cancer center by the National Cancer Institute
• More than 300 cancer researchers on faculty
• 462,886 square feet of research space
• #13 in National Institutes of Health funding (YSM)
• #18 in National Cancer Institute funding
• $96 million in cancer research funding
• $49 million in funding from the National Cancer Institute
• 96 National Cancer Institute funded projects
• 17 members of the National Academy of Sciences
• 16 members of the National Academy of Medicine
• 10 Howard Hughes Medical Investigators
• 4588 cancer research publications; 1096 in high impact journals (July 2012-July 2019)
Sarah B. Goldberg, MD, MPH, Principal Investigator, associate professor of medicine, Yale Cancer Center
Call to Action: Investigator Goldberg suggests that PD-L1 expression correlated with better, longer responses. But they cannot be sure and they need to conduct more clinical trials to confirm.