FDA approves new drug for GEP-NETS

The US Food and Drug Administration (FDA) recently approved a new drug for the treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Lutetium Lu 177 dotatate (Lutathera; Advanced Accelerator Applications) is the first radiopharmaceutical approved for the treatment of GEP-NETs.

“GEP-NETs are a rare group of cancers with limited treatment options after initial therapy fails to keep the cancer from growing,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval provides another treatment choice for patients with these rare cancers. It also demonstrates how the FDA may consider data from therapies that are used in an expanded access program to support approval for a new treatment.”

GEP-NETs can be present in the pancreas and different parts of the gastrointestinal tract, such as the stomach, intestines, colon, and rectum. It is estimated that approximately one in 27,000 people are diagnosed with GEP-NETs each year.

Lutetium Lu 177 dotatate works by binding to somatostatin receptors. After binding, the drug enters the cell, allowing radiation to damage the tumor cells.

Two studies supported the approval. The first was a randomized clinical trial of 229 patients with a type of advanced somatostatin receptor-positive GEP-NET. Patients received either lutetium Lu 177 dotatate in combination with the drug octreotide or octreotide alone. The study measured progression-free survival, or the length of time the tumors did not grow after treatment. Progression-free survival was longer for patients taking the new drug with octreotide compared with patients who received octreotide alone.

The second study was based on data from 1,214 patients with somatostatin receptor-positive tumors, including GEP-NETS, who received lutetium Lu 177 dotatate at a single site in the Netherlands. Complete or partial tumor shrinkage was reported in 16% of a subset of 360 patients with GEP-NETs who were evaluated for response by the FDA.

Patients initially enrolled in the study received the drug as part of an expanded access program. The program allows patients with serious or immediately life-threatening diseases or conditions who lack therapeutic alternatives to gain access to investigational drugs.

Common side effects included lymphopenia; increased GGT, AST and/or ALT; vomiting; nausea; hyperglycemia; and hypokalemia.

Serious side effects included myelosuppression, secondary myelodysplastic syndrome, leukemia, renal toxicity, hepatotoxicity, neuroendocrine hormonal crises, and infertility. Lutetium Lu 177 dotatate can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception. As patients taking the drug are exposed to radiation, exposure to other patients, medical personnel, and household members should be limited in accordance with radiation safety practices.

The drug was granted Priority Review, under which the FDA takes action on an application within 6 months when the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing, or preventing a serious condition. It was also granted an Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.