Lanreotide, a somatostatin analog, significantly prolonged progression-free survival in a phase III trial of patients with advanced enteropancreatic neuroendocrine cancer, potentially leading to the first approved treatment for certain forms of the disease.

Treatment with a somatostatin analog significantly prolonged progression-free survival (PFS) in a large phase III trial of patients with advanced enteropancreatic neuroendocrine cancer, potentially leading to the first approved therapy for certain tumors.

In the Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors (CLARINET), more than 200 patients with metastatic neuroendocrine cancer—tumors that start from endocrine cells most commonly in the gastrointestinal system or pancreas but also in the lungs and other areas—in 14 countries were randomly assigned to receive a monthly injection of lanreotide (Somatuline; Ipsen) or placebo. At 24 months, the rate of PFS was significantly higher in the lanreotide group (65% vs. 33%), and the risk of disease progression within 96 weeks of the first dose was reduced by 53%, according to results published in The New England Journal of Medicine.

“This is one of the most important studies for neuroendocrine cancers in a long time,” says Edward M. Wolin, MD, co-director of the Carcinoid and Neuroendocrine Tumor Program at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute in Los Angeles, CA, and a study co-author. “It will potentially lead to a whole new direction of treatment for pancreatic neuroendocrine tumors.”

Based on the findings, Ipsen has filed a supplemental new drug application for lanreotide to treat enteropancreatic neuroendocrine tumors. The drug, which is more commonly used to treat symptoms of hormone hypersecretion, was previously approved for the treatment of acromegaly.

CLARINET is the first randomized trial to demonstrate that a somatostatin analog may be effective in slowing the growth of advanced (grade 1 or 2) neuroendocrine tumors. The findings build on results from a smaller previous trial, PROMID, which showed a significantly prolonged time to tumor progression with the somatostatin analog octreotide in patients with grade 1 midgut tumors.

“It's never been convincingly proven that these drugs can stop tumors from growing,” says Wolin. “In our study, lanreotide stopped cancer in its tracks in people with metastatic inoperable disease.”

Lanreotide's favorable safety profile also makes it an attractive potential treatment option for neuroendocrine tumors, adds Wolin. The drug has low toxicity and produces very few side effects compared with chemotherapy.

The study did not show a significant difference in overall survival (OS) between the two groups after 2 years. However, OS is affected by other factors, such as crossover from placebo to active treatment by patients with disease progression, the authors note.

Follow-up studies are looking at the durability of lanreotide's effects on tumor growth as well as its effectiveness in combination with complementary molecular therapies in patients with a higher risk of progression than those in the CLARINET trial.

There have been relatively few rigorous studies of therapies for neuroendocrine tumors due to the perceived rarity of the disease, says Wolin. However, incidence of the disease has increased rapidly over the last 30 years, and it now affects an estimated 110,000 patients annually in the United States.

“There is a tremendous unmet need because there is currently no FDA-approved drug for neuroendocrine tumors that start in the intestine,” he says. “We hope that in the near future this will become standard treatment for neuroendocrine cancer.”