Afinitor-Sandostatin LAR Depot combination extends median PFS in patients with advanced carcinoid tumors

Novartis Pharmaceuticals CorporationOct 11 2010

A Novartis Pharmaceuticals Corporation ("Novartis") Phase III study of Afinitor® (everolimus) tablets in combination with Sandostatin® LAR Depot (octreotide acetate for injectable suspension) extended median progression-free survival (PFS), or time without tumor growth, in patients with advanced carcinoid tumors compared to taking octreotide LAR alone. The study, RADIANT-2 (RAD001 In Advanced Neuroendocrine Tumors), was presented at the 35th European Society for Medical Oncology (ESMO) Congress and is part of the largest clinical trial program in patients with advanced neuroendocrine tumors (NET).

Everolimus is not approved in this patient population. Octreotide LAR is indicated for long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors and long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors in patients in whom initial treatment with immediate-release octreotide acetate injection has been shown to be effective and tolerated. In patients with carcinoid syndrome and VIPomas, the effect of octreotide acetate and octreotide LAR on tumor size, rate of growth and development of metastases has not been determined.

The study did not meet its primary endpoint of PFS based on central radiologic review of the data.

Further analyses of the study data were conducted using a well-established statistical model to adjust for imbalances in baseline characteristics between the two treatment arms and inconsistencies between the review of radiology scans for disease progression. The results show that everolimus plus octreotide LAR provided a statistically significant reduction in the risk of disease progression by 40%.

Patients examined in the study had advanced carcinoid tumors that originated in the gastrointestinal (GI) tract, lungs and other locations in the body. Carcinoid tumors, the most common form of NET, are a rare cancer that can cause symptoms such as flushing and diarrhea. Most patients with carcinoid tumors are not diagnosed until their disease has advanced, meaning the cancer has spread to other parts of the body and has become more difficult to treat. Patients with advanced carcinoid tumors usually have a five year survival rate of less than 35%.

"A key goal of treating patients with advanced NET is to extend time without tumor growth," said Professor Marianne Pavel, MD, Leader, Section for Neuroendocrine Tumors and Clinical Trial Unit in Neuroendocrine Tumors, Charite University Medicine, Berlin, and primary investigator of the RADIANT-2 trial. "This Phase III study is important because it shows that everolimus plus octreotide LAR may provide a viable new treatment approach for patients with advanced NET, where there is a high unmet need."

Results from the Phase III RADIANT-3 trial, which were also presented at the ESMO Congress, show that everolimus more than doubled median time without tumor growth from 4.6 to 11.0 months when compared with placebo in patients with advanced pancreatic NET.

"Results from the RADIANT trials, the largest and broadest in patients with advanced NET, will form the basis for regulatory filings later this year and demonstrate the ongoing commitment Novartis has to the NET community," said Herve Hoppenot, President, Novartis Oncology.