Sandostatin LAR (octreotide acetate suspension for injection) demonstra -ted antitumour benefit in patients with metastatic neuroendocrine tumours (NETs) of the midgut, according to interim data presented at the 2009 Gastrointestinal Cancer Symposium of the American Society of Clinical Oncology.
After six months of treatment, patients receiving Sandostatin LAR had a 66 per cent in risk of disease progression compared to patients taking placebo (P=0.000072). This reduction is based on findings that Sandostatin LAR halted tumour growth in 69 per cent of patients, compared with 39 per cent of patients receiving placebo. Patients who took Sandostatin LAR had no tumour progression for a median of 14.3 months, compared to six months for patients on placebo. This beneficial effect was seen in patients with either functioning (hormone secreting) or non-functioning (non-secreting) NETs.
The findings are from a phase IIIb, multicentre, prospective, randomized, placebo-controlled, double-blind, study called PROMID (Placebo-controlled prospective Randomized study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic neuroendocrine MIDgut tumours).
"Sandostatin LAR has a proven track record of treating the severe diarrhoea and flushing associated with neuroendocrine tumours and now this study demonstrates that Sandostatin LAR also helps control tumour growth in patients with metastatic neuroendocrine tumours of the midgut," said PROMID Lead Investigator Professor Rudolf Arnold, Philipps-University Marburg, Germany. "In addition, we saw the greatest benefit in those patients who were newly diagnosed and who had fewer liver metastases (<10% hepatic tumour load), underscoring the importance of early treatment."
This is the first placebo-controlled study to confirm previous findings that suggested treatment with Sandostatin LAR could achieve stabilization of tumour growth in up to 50 per cent of patients with NETs of various origin.
"In recent years, a growing body of evidence has suggested that Sandostatin LAR provides antitumour effects, but these are the first data to confirm this effect from a well-designed, prospective, placebo-controlled study," said David Epstein, president & CEO of Novartis Oncology. "Studies are also underway to evaluate the benefit of combination therapy of Sandostatin LAR with our investigational mTOR inhibitor, RAD001, in patients with various types of NETs."
The term "neuroendocrine tumour" or "NET," as defined by the World Health Organization, refers to a diverse mixture of tumours originating from the interface between the endocrine (hormonal) system and the nervous system, and includes carcinoid tumours and pancreatic NETs. Treatment options for patients with NETs are limited, with surgery being the only chance for cure. When the tumour is inoperable, the objectives of treatment are to control the potentially life-threatening symptoms (syndromes) caused by hormone secretion and to extend patient survival by reducing tumour volume or by stopping the tumour from growing. The PROMID study included only patients with well-differentiated metastatic midgut tumours.
PROMID is a phase IIIb study conducted at 18 sites in Germany to evaluate the antitumour effect of Sandostatin LAR in patients with NETs. The study included 85 patients who were treated with either Sandostatin LAR or placebo until tumour progression. All patients in the study were treatment-naïve, had locally inoperable or metastatic NETs with the primary tumour within the midgut, were without curative therapeutic options and had tumours that were functionally active (i.e. tumours that secrete various hormones and bioactive amines, causing symptoms such as diarrhoea or flushing) or inactive. The study was sponsored by Novartis.
The safety findings observed in the PROMID study were consistent with those seen in previous studies of Sandostatin LAR in patients with NETs. The most frequently observed serious adverse events affected the gastrointestinal tract (octreotide LAR arm: n=6, placebo arm n=8), the hematopoetic system (octreotide LAR arm: n=5, placebo arm n=1) and the general health status (fatigue, fever; octreotide LAR arm: n=7, placebo arm n=2). Serious adverse events occurred in 11 Sandostatin LAR treated patients and 10 placebo recipients. Discontinuation of treatment because of adverse effects occurred in two of 42 patients in the octreotide LAR and in zero of 43 patients in the placebo arm.
Sandostatin LAR is a long-acting, injectable depot dosage formulation of octreotide acetate, a somatostatin analog that exerts similar pharmacologic effects on the human body as the natural hormone somatostatin. However, octreotide is even more potent than somatostatin at inhibiting growth hormone, glucagon and insulin. Based on these attributes, octreotide has been used to treat the clinical syndromes associated with NET. In addition, octreotide substantially reduces and in many cases can normalize growth hormone and/or IGF-1 levels in patients with acromegaly, a disease caused by a pituitary adenoma.
Sandostatin, the immediate release formulation of octreotide acetate for subcutaneous injection or intravenous infusion was first approved in New Zealand in December 1987. In June 1995, the long-acting depot formulation, which Novartis markets as Sandostatin LAR was approved in France. Through more than a decade and 600,000 patient years of experience, Sandostatin Injection/Sandostatin LAR has achieved a long-standing track record of sustained efficacy with a well-established safety profile.