A nuclear-medicine therapy approved by the U.S. Food and Drug Administration (FDA) in 2018 has led to improved survival and quality of life for patients with advanced gastrointestinal or pancreatic neuroendocrine tumors who would otherwise have few effective treatment options. UCLA has administered the therapy to nearly 100 patients.
Martin Allen-Auerbach, MD, medical director of the UCLA Nuclear Medicine Clinic, explains that the drug, 177Lu-DOTATATE, is part of an emerging cancer-treatment strategy known as theranostics. Theranostics utilizes diagnostic imaging to ensure that a specific therapeutic target — such as the somatostatin receptor commonly found in neuroendocrine tumors — is being expressed by cancer cells and then introduce a therapeutic isotope that will treat the tumor. In addition to employing this approach to treat neuroendocrine tumors, UCLA is playing a lead role in research into the effectiveness of theranostics to treat prostate cancer.
“What’s exciting about this strategy is that we are linking imaging directly with a therapeutic agent,” says Andrew Quon, MD, professor of molecular and medical pharmacology. Drs. Allen-Auerbach and Quon are both members of UCLA’s Ahmanson Translational Imaging Division, which includes experts in the diagnosis and treatment of neuroendocrine tumors.
Prior to FDA approval, UCLA was among the few expanded-access investigational sites for 177Lu-DOTATATE in the United States. UCLA remains one of the most experienced sites in the country.
Neuroendocrine tumors are rare, slow- growing tumors that can develop in hormone- producing cells of the neuroendocrine system. Neuroendocrine tumors most commonly arise in the gastrointestinal tract and pancreas.
Dr. Quon explains that since most cancer cells utilize glucose, the standard imaging tracer for PET/CT scanning uses a radioactive form of glucose (called FDG) to image cancer. But because neuroendocrine tumors grow slowly, they typically do not metabolize glucose at a high rate and therefore cannot be imaged effectively with FDG. To address this, an imaging agent called
68Ga-DOTATATE was developed to target somatostatin receptors rather than glucose metabolism, enabling the PET/CT scan
to localize and stage the neuroendocrine tumor. “This imaging agent is a significant improvement over prior agents and allows us to plan the most appropriate therapy for our patients who have neuroendocrine tumors,” Dr. Allen-Auerbach says.
177Lu-DOTATATE adds a therapeutic to the diagnostic approach: Imaging of the neuroendocrine cancer with the radioactive tracer 68Ga-DOTATATE is followed by treatment with 177Lu-DOTATATE to kill the cancer cells. “Once we see that the cancer expresses somatostatin receptors, we can go back to the patient and treat his disease,” Dr. Quon explains.
177Lu-DOTATATE is administered on an outpatient basis in four doses given at eight- week intervals, usually with only minor side effects. In the clinical trial that led to approval of the drug, approximately two-thirds of patients experienced either stabilization of their disease or shrinkage of their tumors, with improv ed quality of life. UCLA has experienced similar results with patients treated so far.
The drug currently is indicated only for inoperable or metastatic neuroendocrine tumors that continue to progress following first-line therapies. “Because this drug has been so effective in patients with advanced disease, research is underway to determine whether or not it should be used earlier,” Dr. Quon says.