Long-Term Data Support Safety of Lanreotide in Advanced Neuroendocrine Tumors

Charles Bankhead

April 2017, Vol 8, No 2 - Neuroendocrine Tumors

San Francisco, CA—Pooled data from 2 randomized clinical trials and several open-label extension studies confirmed the safety and quality-of-life effects of long-term (>12 months) use of the somatostatin analog lanreotide (Somatulin Depot) for advanced neuroendocrine tumors (NETs), including functioning and nonfunctioning NETs, reported Alexandria T. Phan, MD, Medical Oncologist, University of New Mexico Cancer Center, Albuquerque, and colleagues, at a poster session at the 2017 Gastrointestinal (GI) Cancers Symposium.

The majority of patients had GI adverse events, but treatment-related adverse events were infrequent during the double-blind and open-label treatment with lanreotide.

Combined with the efficacy data from randomized clinical trials, the safety findings confirmed a favorable benefit–risk ratio for long-term treatment with lanreotide, the investigators noted.

“This synthesis of safety data from randomized controlled trials and longer-term studies of lanreotide autogel/depot shows a consistent safety profile, observed alongside stability or modest improvement in quality of life,” concluded Dr Phan and colleagues. “Together with the efficacy reported in the separate studies, this analysis supports the long-term use of lanreotide autogel/depot both for cancer symptom control and tumor control in advanced NETs,” they added.

A 2014 randomized, placebo-­controlled clinical trial of lanreotide in patients with grade 1 or 2 NETs demonstrated a doubling of 24-month progression-free survival (PFS) and a significant improvement in the median PFS. A 2016 randomized, placebo-controlled clinical trial demonstrated significant improvement in treatment success with lanreotide in patients with carcinoid syndrome. Open-label extensions of these 2 studies provided further long-term data.

Previous studies with lanreotide had demonstrated the drug’s safety and tolerability. However, data from the 2 randomized clinical trials, their long-term open-label extensions, and 3 other open-label extension studies afforded an opportunity to revisit the safety profile of lanreotide in patients with functioning or nonfunctioning NETs.

This analysis involved 378 patients who received lanreotide in the 2 randomized clinical trials and 3 open-label extension studies, as well as 160 patients who initially received placebo. Approximately 50% of the patients had no previous exposure to a somatostatin analog, and approximately 50% had functioning NETs.

In one of the randomized studies, diarrhea and flushing were assessed as end points. As a result, those adverse events were excluded from the updated analysis of the safety and tolerability of lanreotide. In the 2 randomized clinical trials, investigators assessed quality of life based on surveys from the European Organisation for Research and Treatment of Cancer.

Adverse Events

Overall, 55.8% of patients who received lanreotide and 45.6% of patients who received placebo had GI adverse events. The incidence of GI adverse events did not differ between patients who received lanreotide in the randomized studies and in the open-label extension studies.

Other common adverse events associated with lanreotide therapy included general or injection-site (42.1%) events, infection (36.2%), musculoskeletal or connective tissue (32.5%) events, metabolism or nutrition (28.8%) events, and nervous system (27.5%) events. Overall, the frequency of the adverse events in patients who received lanreotide did not differ markedly from those who received placebo.

The most common adverse events included abdominal pain (23.0%), vomiting (14.6%), headache (13.5%), nausea (13.0%), fatigue (12.2%), upper abdominal pain (11.9%), cholelithiasis (10.8%), asthenia (10.8%), back pain (10.6%), and constipation (10.1%). There were no consistent or notable differences in the adverse events between patients who received lanreotide and those who received placebo.

Overall, treatment-related adverse events in the randomized clinical trials and in the open-label extension studies occurred more often with lanreotide than with placebo, but all with an incidence of <10%. Abdominal pain (9.5%) was the most frequent treatment-related event in patients who received lanreotide, followed by cholelithiasis (8.5%), injection-site pain (7.9%), and nausea (5.6%).

The randomized clinical trials showed no differences in quality-of-life scores between patients who received lanreotide and those who received placebo. However, data from the open-label extension studies provided some evidence of improvement in certain quality-of-life outcomes with lanreotide.