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ECC 2015: Advanced Gastrointestinal Neuroendocrine Tumors and Results From the NETTER-1 Trial

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Key Points

  • At the time study data were analyzed, the median progression-free survival for 177Lu-DOTATATE had not been reached; it was defined as 8.4 months in patients who received octreotide LAR alone.
  • 177Lu-DOTATATE has a good safety profile and offers patients a good quality of life.
  • By the use of scintigraphy, 177Lu-DOTATATE enables researchers to identify patients who are eligible for treatment and who should respond positively to it.

Results from a multicenter randomized international trial of an innovative treatment show a marked improvement in the length of time patients with midgut neuroendocrine tumors experience progression-free survival, researchers reported at the 2015 European Cancer Congressin Vienna, Austria, on September 27 (Abstract 6LBA).

Philippe Ruszniewski, MD, Head of the Department of Gastroenterology-Pancreatology at Beaujon Hospital and Professor at Paris Diderot University, presented the results of the NETTER-1 phase III trial of the investigational agent lutetium Lu-177 dotatate (Lutathera), which show a progression-free survival unmatched in this type of cancer.

“Because these patients have a real unmet medical need, this is particularly pleasing for us,” Dr. Ruszniewski said.

Lu-177 dotatate is a member of the family of novel treatments called peptide receptor radionuclide therapies, which involve targeting tumors with radiolabelled somatostatin analog (SSA) peptides. The technique belongs to the larger family of molecular nuclear medicine, where trace amounts of active substances, or radiopharmaceuticals, are used to create images and to treat various diseases—including cancer. SSAs are widely used in gastrointestinal neuroendocrine tumors to reduce symptoms such as diarrhea.

Trial Results

The trial recruited 230 patients from 36 sites in eight European countries and 15 centers in the United States. All patients had midgut neuroendocrine tumors that had metastasized, and had already undergone SSA treatment. They were randomly assigned to receive either Lu-177 dotatate combined with the somatostatin octreotide LAR (the current standard of care in midgut neuroendocrine tumors) or octreotide LAR alone. The primary endpoint of the trial was progression-free survival, while secondary endpoints included overall survival, safety, and quality of life, among others.

“Our results confirmed data from phase I and II trials,” Dr. Ruszniewski said. “At the time we analyzed the data, the median progression-free survival for [Lu-177 dotatate] had not been reached, whereas we could define it as 8.4 months in patients who received octreotide LAR alone. Results so far show that patients on [Lu-177 dotatate] are achieving extra time without their disease progressing. This kind of progression-free survival is rarely achieved in cancer. We also have been able to see that [Lu-177 dotatate] has a good safety profile, and offers these patients a good quality of life,” he noted.

“From a payer’s point of view, there are significant advantages too. By the use of a scintigraphy, [Lu-177 dotatate] enables us to identify the patients who are eligible for treatment and who should respond positively to it. This should lead to substantial savings and ensure that most patients who receive the treatment are likely to respond.”

Lu-177 dotatate is injected intravenously, and octreotide LAR by deep intragluteal injection. Patients in the Lu-177 dotatate group receive four doses over 8 weeks, plus 30 mg of octreotide LAR every 28 days. Patients in the octreotide LAR–alone group receive 60 mg of the drug every 4 weeks. Progression-free survival is analyzed every 12 weeks, and patients remain in the study until their disease progresses, there is unacceptable toxicity, or they wish to withdraw for their own reasons.

Rare Disease

Midgut neuroendocrine tumors are rare, with an incidence generally estimated to be around 5 in every 100,000 cancers. All neuroendocrine tumors are classified as rare diseases by regulatory authorities in the European Union and United States.

“This means that there are few drugs available to treat these patients, and that is why we are particularly excited to have found something with what appears to be such a long-lasting effect,” said Dr. Ruszniewski. “Now, apart from making the drug available through submitting it for approval by the regulatory authorities, we would like to see additional studies investigating its efficacy in other types of neuroendocrine tumors—for example, pancreatic and bronchial,” he concluded.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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