FDA Approves Lanreotide for Gastroenteropancreatic Neuroendocrine Tumors

Alexandria Phan, MD

The FDA has approved lanreotide (Somatuline Depot Injection) for the treatment of patients with unresectable, well or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), based on findings from the phase III CLARINET study.

The treatment was approved under the FDA's priority review program, based on a significant extension in progression-free survival (PFS). According to results published in The New England Journal of Medicine, treatment with the somatostatin analog lanreotide improved PFS by 53% compared with placebo for patients with grade 1 or 2 GEP-NETs. Moreover, quality of life was found to be similar between patients treated with lanreotide and placebo.

“Somatuline is the first somatostatin analog to demonstrate a statistically significant improvement in progression-free survival, a clinically significant endpoint in oncology which measures how long the patient continues to live with the disease without it getting any worse,” Alexandria Phan, MD, the director of GI Medical Oncology at Houston Methodist, said in a statement. “Somatuline offers a new weapon in our fight against this deadly disease.”

In the CLARINET study, 204 patients were randomized to lanreotide at 120 mg (n = 101) or placebo (n = 103). Treatment was administered once a month for 24 months. The primary endpoint of the study was PFS, with secondary endpoints focused on overall survival (OS) and quality of life.

Patients had tumors that were located in the pancreas (44%), midgut (36%), hindgut (7%), and unknown locations (13%). Most patients had stable disease (96%) and were treatment-naïve (84%). In total, 33% of patients had a hepatic tumor load >25%.

In the study, PFS extended over 22 months in the lanreotide arm; however, the median was not reached at the time of the analysis. The median PFS in the placebo arm was 16.6 months (HR = 0.47; 95% CI, 0.30-0.73; P <.001). At the end of 24 months, the estimated PFS rate was 65% in the lanreotide arm compared with 33% with placebo.

The HR for PFS in patients with midgut tumors (n = 73) was 0.35 for lanreotide and placebo. Patients with hindgut tumors (n = 14) experienced better PFS outcomes with placebo compared with lanreotide (HR = 1.47). For patients with tumors located in the pancreas (n=91), the HR for PFS was 0.58, favoring lanreotide.

After the 24-month study period, patients in the placebo arm were allowed to crossover to receive lanreotide. In total, 47 patients randomized to placebo received lanreotide during the follow-up period. As a result of this crossover, a significant difference in OS was not demonstrated with lanreotide.

The most common adverse events with lanreotide versus placebo were abdominal pain (34% vs 6%), musculoskeletal pain (19% vs 2%), vomiting (19% vs 2%), headache (16% vs 0%), injection site reaction (15% vs 0%), hyperglycemia (14% vs 0%), hypertension (14% vs 1%), and cholelithiasis (14% vs 1%). For patients who developed cholelithiasis, 4 patients had new gallbladder sludge (3% vs 1%) and 10 patients had new lithiasis (7% vs 3%). Severe adverse events occurred in 26% of patients.

“Somatuline is the first and only treatment with a statistically significant progression-free survival benefit approved by the FDA for patients as an antitumor therapy in the treatment of gastrointestinal and pancreatic neuroendocrine tumors.,” Cynthia Schwalm, president and CEO of Ipsen North America, said in a press release. "This is a significant step forward in our mission to develop and deliver innovative therapies to treat serious illnesses.”

The FDA initially approved lanreotide in 2007 as a long-term treatment for patients with acromegaly. Traditionally, somatostatin analogs have been used for symptom control in patients with NETs.