Phase II study of lanreotide autogel in Japanese patients with unresectable or metastatic well-differentiated neuroendocrine tumors

• Published in: Investigational new drugs Vol. 35; no. 4; pp. 499 - 508
• Main Authors: Ito, Tetsuhide, Honma, Yoshitaka, Hijioka, Susumu, Kudo, Atsushi, Fukutomi, Akira, Nozaki, Akira, Kimura, Yasutoshi, Motoi, Fuyuhiko, Isayama, Hiroyuki, Komoto, Izumi, Hisamatsu, Seiichi, Nakajima, Akihiro, Shimatsu, Akira
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2017; Springer Nature B.V
• Subjects: Aged; Antineoplastic Agents - adverse effects; Antineoplastic Agents - blood; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Asian Continental Ancestry Group; Confidence intervals; Diabetes mellitus; Disease-Free Survival; Fas antigen; Feces; Female; Foregut; Gastrointestinal Neoplasms - drug therapy; Gastrointestinal Neoplasms - metabolism; Gels; Hindgut; Humans; Injection; Kaplan-Meier Estimate; Lungs; Male; Medicine; Medicine & Public Health; Metastases; Middle Aged; Midgut; Multiple endocrine neoplasia; Neuroendocrine tumors; Neuroendocrine Tumors - drug therapy; Neuroendocrine Tumors - metabolism; Oncology; Pancreas; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Patients; Peptides, Cyclic - adverse effects; Peptides, Cyclic - blood; Peptides, Cyclic - pharmacokinetics; Peptides, Cyclic - therapeutic use; Pharmacokinetics; Pharmacology; Pharmacology/Toxicology; Phase II Studies; Safety; Somatostatin; Somatostatin - adverse effects; Somatostatin - analogs & derivatives; Somatostatin - blood; Somatostatin - pharmacokinetics; Somatostatin - therapeutic use; Studies; Survival; Treatment Outcome; Tumors; Phase II; Neuroendocrine tumor; Japanese; Lanreotide; Somatostatin analog
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-017-0466-8

Summary Background Lanreotide is a long-acting somatostatin analog with demonstrated efficacy against enteropancreatic neuroendocrine tumor (NET) in the phase III (CLARINET) study. Materials and Methods In this single-arm study, Japanese patients with grade (G) 1/G2 NET received lanreotide (120 mg/4 weeks) for 48 weeks. Those who completed the study were enrolled in a long-term extension study. The primary endpoint was the clinical benefit rate (CBR) defined as a complete response, partial response (PR), or stable disease (SD) over 24-weeks. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), safety, and pharmacokinetics. Results Thirty-two patients were recruited at 10 sites. The full analysis set (FAS) comprised 28 patients. Primary tumors were located in pancreas (12 patients), foregut (non-pancreas, lung; 1), midgut (2), hindgut (8), and unknown (5). Four patients had gastrinoma of the functional NET, and 3 had multiple endocrine neoplasia type 1. In the FAS, 39.3% had progressive disease at baseline. The CBR at 24 weeks was 64.3% (95% confidence interval; CI: 44.1–81.4), and median PFS was 36.3 weeks (95% CI: 24.1–53.1). PR was confirmed in 1 patient at 60 weeks during the extension study (ORR: 3.6%). Frequent adverse events related to lanreotide included injection site induration (28.1%), faeces pale (18.8%), flatulence (12.5%), and diabetes mellitus (12.5%). Conclusions The efficacy and safety of lanreotide in this study indicated its usefulness as a treatment option for Japanese NET patients. Trial registration: JapicCTI-132,375, JapicCTI-142,698.