Effect of Open-Label Everolimus After Disease Progression in Patients with Advanced Neuroendocrine Tumors: A RADIANT-2 Analysis Abstract #490

Introduction: In the RADIANT-2 study (NCT00412061), Everolimus + Octreotide LAR (E+O) resulted in a clinically meaningful increase in median progression-free survival (PFS; by adjudicated central review) of 5.1 months v. placebo + Octreotide LAR (P+O) in patients with advanced NET with a history of carcinoid syndrome. Investigator-assessed PFS was 12.0 months for E+O compared with 8.6 months for P+O, respectively. On radiologically confirmed disease progression, P+O patients could cross over to open-label E+O.
Aim(s): To present the outcomes of P+O patients who crossed over to open-label E.
Materials and methods: Four-hundred and twenty-nine patients were randomly assigned: 216 to E (10 mg/d) + O (30 mg IM q 28 d) and 213 to P+O. After progression, crossover occurred for 124 patients.
Conference: 9th Annual ENETS Conference (2012)
Category: Clinical
Presenting Author: Dieter Hörsch

To read results and conclusion, please login ...

Further abstracts you may be interested in

#18 Long-acting release octreotide induce complete response in type 1 gastric carcinoid tumors
Introduction: Gastric endocrine tumors (GET) are increasingly recognized due to expanding indications of upper gastrointestinal endoscopy. Often silent and benign, GET may also be aggressive when sporadic and may sometimes mimic the course of gastric adenocarcinoma. Current incidence of GETs is estimated at around 8% of digestive endocrine tumors. Yearly age-adjusted incidence is around 0.2 per population of 100,000. Gastric carcinoids (ECLomas) develop from gastric enterochromaffin-like cells (ECL cells) in response to chronically elevated gastrin. Type 1 tumors (ECLomas in the course of atrophic gastritis) may occur in conditions of achlorhydria secondary to auto-immune atrophic fundic gastritis. It occurs mostly in women and they are non-functioning tumors, typically found during upper GI endoscopy performed for dyspepsia. ECLomas present frequently as multiple polyps, usually < 1 cm in diameter in the gastric fundus. Type 1 tumors are almost exclusively benign lesions with little risk of deep invasion of the gastric parietal wall. The neoplastic ECL cells become progressively dedifferentiated with an increasing number of Ki-67 immunoreactive (IR) cell nuclei. In addition, there is a substantial decrease in argynophil and IR NE cells that can be visualized by conventional methods. ECLomas secondary to hypergastrinemia should be closely followed for signs of clinical and histopathological tumor progression. Such ECLomas deserve early, active, radical surgical treatment.
Traditionally, gastric carcinoid type 1 (GCA1s) are endoscopically or surgically removed, depending on the number, appearance and size of the tumors. Antrectomy, with surgical excision of the majority of the G cells, is thought to facilitate regression of these tumors by removing the source of excessive gastrin secretion; however, the long-term benefits of antrectomy still remain uncertain. Although proton pump inhibitors are effective in reducing hypergastrinemia-induced gastric acid hypersecretion in GCA2, they do not affect ECL-cell hyperplasia, and therefore their role in GCA1 is limited. Moreover, in selected cases, significant reduction of hypergastrinemia does not prevent development of ECL carcinoid, suggesting that, in addition to hypergastrinemia, other pathogenic or genetic factors may be involved. Treatment with somatostatin analogues (SSA) might impede ECL-cell hyperplasia by suppressing gastrin secretion and/or by a direct anti-proliferative effect on ECL cells. Treatment with SSAs in GCA1 leads to a substantial tumor load reduction, with a concomitant decrease of serum gastrin levels. Published data indicate an important anti-proliferative effect of SSA on ECL cells, providing clinical benefit and obviating, at least temporarily, the need for invasive therapies for GCA1. Morphometric studies demonstrated that, while antrectomy specifically decreased the volume of ECL cells versus the total volume of endocrine cells, octreotide reduces the overall endocrine cell volume. Although the number of treated patients is small, it has been suggested that SSA may exert important anti-proliferative effects either directly, by inhibiting ECL-cells proliferation, or indirectly through suppression of gastrin hypersecretion.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: MD Ricardo Caponero
#19 Antitumor activity of Pasireotide (SOM230) alone and in combination with Everolimus (RAD001) in DU-145 human prostate cancer model
Introduction: Pasireotide (SOM230) is a novel multi-receptor ligand somatostatin analogue with high affinity for somatostatin receptor subtypes sst1,2,3 and sst5. Like octreotide, which binds primarily to sst2, it inhibits hypersecretion of hormones from patients with functional pituitary tumors and gastroenteropancreatic neuroendocrine (GEP/NET) tumors. In addition, tumor shrinkage has been observed with both compounds in patients with acromegaly, Cushing’s disease and GEP/NETs, but its tumor-reducing mechanism of action has so far not been revealed. In patients with breast and liver cancer, octreotide had little or no antitumor activity.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: Dr. Herbert A. Schmid
#55 Metronomic combination therapy including temozolamide, bevacizumab and somatostatin analogue for the treatment of malignant gastroenteropancreatic neuroendocrine tumors
Introduction: Malignant gastroenteropancreatic neuroendocrine tumors (GEPNETS), mainly carcinoids, are not considered to be particularly chemotherapy-sensitive to conventional chemotherapeutic schemes. Long-standing evidence suggests these tumors to be highly vascularised and responsive to antiangiogenic strategies. Newest reports demonstrate benefit by the use of temozolamide, an oral alkylating agent similar to intravenous dacarbazine. The DNA repair enzyme O6-alkylguanine–DNA alkyltransferase (AGAT) confers cancer cell resistance to O6-alkylating agents such as temozolamide through its ability to remove methyl/alkyl groups from the O6-position of guanine, thus correcting drug-induced DNA damage.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: DR Anna Koumarianou
#108 Everolimus (RAD001) induces tumor response in patients with medullary thyroid cancer: an in vivo and in vitro study
Introduction: Medullary thyroid cancer (MTC) is a neuroendocrine tumor (NET) of the thyroid C cells which is known to express somatostatin receptors. Octreotide, a somatostatin analogue exerting both antisecretory and antitumor activity in different types of NETs, has shown low efficacy in MTC. Everolimus (RAD001), an inhibitor of mTOR, has shown antitumor effects in patients with NETs and synergistic effects when combined with octreotide. Until recently, RAD001 has never been evaluated in MTC.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: MD, PhD Antongiulio Faggiano
#114 Downstaging of a gastroenteropancreatic neuroendocrine tumor after combination therapy of temozolomide, Bevacizumab and long-acting somatostatin analogs
Introduction: Patients with gastroenteropancreatic endocrine (GEP) tumors and progressive disease have been treated with several chemotherapeutic regimens with variable responses and considerable toxicity. Recent studies have shown that GEP tumors may respond to therapy with anti-angiogenic agents, mainly as a result of their increased vascularity.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Stavroula Antoniou