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RAD001 Combined With Sandostatin(R) LAR(R) And As Monotherapy Controls Growth Of Rare Pancreatic Neuroendocrine Tumours

April 01, 2017

New data show that combination treatment with RAD001 (everolimus) and Sandostatin® LAR® (octreotide IM) and RAD001 given alone control tumour growth in patients with pancreatic neuroendocrine tumours (NET), a rare and difficult-to-treat form of cancer.1

These results, from the RADIANT-1 (RAD001 In Advanced Neuroendocrine Tumours) study, were presented today at the 33rd European Society for Medical Oncology (ESMO) Congress in Stockholm, Sweden.

In the trial, patients with pancreatic NET who became resistant to chemotherapy were given either daily RAD001 combined with monthly Sandostatin® LAR® or daily RAD001 alone. The results showed that 82% of patients receiving combination therapy and 77% receiving monotherapy had tumours that either decreased in size or remained stable.1

Neuroendocrine tumours (NET) are a rare group of cancers that include pancreatic neuroendocrine tumours (PNET) and carcinoid tumours. NET start in neuroendocrine cells, the specialised nerve cells that produce hormones in the body.2 There are around 1,500 to 2,000 new cases diagnosed each year in the UK.3

"Pancreatic neuroendocrine tumours are extremely rare, difficult to treat and cause debilitating symptoms related to excess hormone production," said Dr Peter Harper, Consultant Medical Oncologist, Guy's and St Thomas'. "Despite chemotherapy treatment, patients do not usually survive longer than 5 years so these data showing the potential of RAD001 to provide tumour shrinkage or stability and to extend time without disease progression are very encouraging."

The study explores the potential of mTOR inhibition for patients with pancreatic NET by examining RAD001 alone or in combination with standard of care treatment, Sandostatin LAR®. RAD001 is a once-daily oral therapy that continuously inhibits the mTOR protein, a central regulator of cell division and tumour blood vessel growth.

Two Phase III trials investigating the use of RAD001 and Sandostatin® LAR® are underway in patients with pancreatic NET and carcinoid tumours. The endpoints will be progression-free survival and overall survival.

References

1. 508PD - A Phase II Trial Of Daily Oral Rad001 (Everolimus) In Patients With Metastatic Pancreatic Neuroendocrine Tumors (Net) After Failure Of Cytotoxic Chemotherapy. Yao, J. et al. Presented at the European Society for Medical Oncology (ESMO) 33rd Congress on 13/9/2008

2. An overview of neuroendocrine tumours. CancerBacup. Last accessed on 12 September 2008 from here.

3. Neuroendocrine tumours. Royal Free Hampstead NHS Trust. Last accessed on 12 September 2008 from here.

RADIANT-1 results

RADIANT-1 is a Phase II international, multi-centre, open label, stratified study of RAD001 in 160 patients with advanced pancreatic NET, who became resistant to prior treatment with cytotoxic chemotherapy. In the monotherapy treatment group, 115 patients received RAD001 alone. In the combination treatment group, 45 patients whose tumours progressed during treatment with Sandostatin LAR continued treatment with the addition of RAD001.1

The primary endpoint of RADIANT-1 was objective response rate (complete response and partial response) in the monotherapy group. The secondary endpoints included response rate in the combination treatment group, as well as response duration, safety and tolerability, progression-free survival (PFS) and overall survival, changes in plasma chromogranin A and pharmacokinetics in both groups.1

Monotherapy treatment group results

Clinical benefit (overall response rate plus stable disease rate) was seen in 77% of patients. The overall response rate for patients who received RAD001 alone was 8% (CI= 3.6-14.3). All confirmed responses were partial responses; there were no complete responses. In addition, 69% of patients experienced stable disease, 14% of patients experienced progressive disease and 10% of patients had an unknown response. Responses were maintained for a median of 10.6 months (8.3-N/A). Further, the results demonstrate PFS of 9.3 months. Median overall survival had not been reached at the time of data evaluation.1

The most frequent adverse events in patients taking RAD001 alone were stomatitis (44%), rash (40%), diarrhoea (37%), fatigue (29%), nausea (26%), vomiting (17%), asthenia (16%), anaemia (12%) and weight decrease (11%).1

Combination treatment group results

Clinical benefit (overall response rate plus stable disease rate) was seen in 82% of patients. The overall response rate for patients who received RAD001 in combination with Sandostatin® LAR® was 4% (CI= 0.5-15.1). All confirmed responses were partial responses; there were no complete responses. The data show that 78% of patients experienced stable disease, 2% of patients experienced progressive disease and 16% of patients had an unknown response. Further, the results demonstrate PFS of 12.9 months. Median overall survival had not been reached at the time of data evaluation.1

The most frequent adverse events in patients taking RAD001 with Sandostatin® LAR® were stomatitis (49%), rash (40%), diarrhoea (29%), fatigue (33%), nausea (33%), vomiting (13%), asthenia (11%), anaemia (18%) and weight decrease (16%).1

About NET

Neuroendocrine tumours (NET) are a rare group of cancers that include pancreatic neuroendocrine tumours (PNET) and carcinoid tumours. NET start in neuroendocrine cells, the specialised nerve cells that produce hormones in the body.2 There are around 1,500 to 2,000 new cases diagnosed each year in the UK.3

About RAD001

RAD001, an oral once daily inhibitor of mTOR, is an investigational drug being studied in multiple tumour types. The safety and efficacy profile of RAD001 has not yet been established in oncology and there is no guarantee that RAD001 will become commercially available for oncology indications. The active ingredient in RAD001 is everolimus.

RAD001 is being studied in two large Phase III studies in advanced NETs (pancreatic NET and carcinoid). In addition to pancreatic NET, RAD001 is being evaluated as a single agent or in combination with existing therapies in renal cell carcinoma, lymphoma, breast, gastric, lung and other cancers, as well as tuberous sclerosis.1

About Sandostatin® LAR®

Sandostatin® LAR® is a long-acting, injectable depot formulation of octreotide acetate, a somatostatin analogue 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 s.c injection or i.v. 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.

Sandostatin® LAR® important safety information

Adverse reactions identified in clinical studies include nausea, abdominal pain, gas, constipation, vomiting, pain on injection, high or low blood sugar levels and slow or irregular heart rate. Many patients developed gallstones, although few patients required treatment.

About Novartis

Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 100,000 associates and operate in over 140 countries around the world.

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