Lu-Dotatate Shows Unprecedented PFS in Midgut NETs

“The radiopharmaceutical Lu-Dotatate (177Lutetium DOTATATE; Lutathera) demonstrated an unprecedented 79% reduction in the risk of progression or death compared with high-dose octreotide LAR (60 mg) in patients with progressive, metastatic midgut neuroendocrine tumors (NETs), according to results from NETTER-1 trial presented by Jonathan Strosberg, MD, at the 2015 NANETS Symposium.”

” ‘The findings were, in my opinion, extraordinarily impressive, the median progression-free survival improved by nearly 80%, which is fairly unprecedented in oncologic studies,’ said Strosberg, a medical oncologist and researcher at the Moffitt Cancer Center. ‘The finding is important because limited therapeutic options exist for such patients, who comprise 20% to 45% of neuroendocrine tumor cases.’ ”

“The NETTER-1 trial is the first prospective, randomized, phase III study for patients with midgut NETs, specifically those in the ileum and cecum. Patients in the trial had progressed on prior therapy with octreotide at 30 mg and had inoperable, somatostatin receptor positive tumors.”

Gene Mutation Signals Poor Prognosis for Pancreatic Tumors

“For patients with pancreatic neuroendocrine tumors, the presence of recently identified mutations in two key genes is a prognostic factor for poor outcome, researchers report.

” ‘We found loss of nuclear expression in about 23% of the tumors that we studied, and this loss of expression was associated with worse tumors from the outset,’ lead investigator Michelle Heayn, MD, a second-year pathology resident at the University of Pittsburgh Medical Center, told Medscape Medical News.

“Pancreatic tumors with neuroendocrine histology frequently respond to chemotherapy and have a more favorable prognosis than the more common pancreatic adenocarcinomas. However, the mutations are associated with worse disease-free and disease-specific survival.”

Lexicon's Telotristat Etiprate Shows Clinical Benefit In Treating Carcinoid Syndrome In Cancer Patients When Added To Standard Of Care

“Lexicon Pharmaceuticals, Inc.’s (Nasdaq: LXRX) telotristat etiprate was shown to have clinical benefit in treating carcinoid syndrome in cancer patients not adequately controlled by long-acting somatostatin analog (SSA) therapy, the current standard of care, according to data from the Phase 3 TELESTAR study presented today at the European Cancer Congress in Vienna, Austria.

“Telotristat etiprate, Lexicon’s most advanced product candidate, met the study’s primary endpoint with clinically meaningful reductions in bowel movement frequency in patients whose condition was not adequately controlled by SSA therapy. Carcinoid syndrome is characterized by frequent and debilitating diarrhea that often prevents patients from leading active, predictable lives, as well as by facial flushing, abdominal pain, heart valve damage and other serious consequences.

” ‘We are pleased with the efficacy and safety results of telotristat etiprate and also with the durability of the response shown in this study,’ said Lexicon Executive Vice President and Chief Medical Officer Pablo Lapuerta, M.D. ‘The data also support that the compound is acting directly on the cause of carcinoid syndrome, by reducing serotonin production within tumor cells.’ “

Results of International Trial Show Promise in Rare, Difficult to Treat Cancer

“Neuroendocrine tumours (NETs) develop in the neuroendocrine system, responsible for producing the hormones that regulate the working of different organs in the body. They are rare, incurable, and treatments for them are limited, especially once they have become advanced. Now an international team of researchers has shown that the use of the mTOR inhibitor, everolimus, can delay tumour growth among both gastrointestinal and lung NETs. This is particularly important for patients with the lung tumours, the researchers say, because there is currently no approved treatment for such cases.

“Reporting on the results of the RADIANT-4 trial, a placebo-controlled, double-blind, phase III study carried out in centres in 13 European countries, Korea, Japan, Canada, and the US, Professor James Yao, MD, Chair of the Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA, will tell the 2015 European Cancer Congress today (Sunday) that the treatment had a significant effect in non-functional NETs. Non-functional NETs either do not secret a hormone, or secrete one that does not cause symptoms, and are therefore often diagnosed later when the cancer has become advanced. ‘About 80% of all NETs are thought to be non-functional, so, unfortunately, late diagnosis is common and poses a major problem for these patients,’ he will say.”

Everolimus Improves Progression-Free Survival for Patients with Advanced, Nonfuctional Neuroendocrine Tumors

“In an international Phase III randomized study, everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), has shown to dramatically improve progression-free survival for patients with advanced, nonfunctional neuroendocrine tumors (NET) of the lung and gastrointestinal tract.

“James C. Yao, M.D., professor and chair, The University of Texas MD Anderson Cancer Center’s Department of Gastrointestinal Medical Oncology, presented the findings today in Vienna, Austria during the presidential session of the European Cancer Congress, co-sponsored by the European Cancer Organisation and European Society for Medical Oncology.

“NETs develop from cells in the neuroendocrine system, which is responsible for producing specific hormones that regulate the functions of different organs in the body. NETs can be slow-growing or aggressive, and are found most commonly in the lungs or gastrointestinal system. Nonfuctional NETs are those that do not secrete a hormone. About 80 percent of all NETs are nonfunctional, and therefore, patients often have few side effects and are diagnosed later, explains Yao.”

Rare Cancer Responds Unusually Well to New Treatment

“Vienna, Austria: Patients with advanced gastrointestinal neuroendocrine tumours (NETs) have limited treatment options and there are few oncologists who are specialised in this relatively rare disease. But now results from a multi-centre randomised international trial of an innovative treatment show a marked improvement in the length of time patients with mid-gut NETs live without the disease getting worse (progression-free survival, or PFS), researchers will report to the 2015 European Cancer Congress today.

“Professor Philippe Ruszniewski, MD, Head of the Department of Gastroenterology-Pancreatology, Beaujon Hospital, Clichy, France, who is also a Professor at Paris Diderot University, will tell the Congress that results of the NETTER-1 phase III trial of 177Lu-DOTATATE (Lutathera) show a PFS that has never been shown before in this type of cancer. “Because these patients have a real unmet medical need, this is particularly pleasing for us,” he says.

“Lutathera is a member of the family of novel treatments called Peptide Receptor Radionuclide Therapy (PRRTs) which involve targeting tumours with radiolabelled somatostatin analogue (SSA) peptides. The technique belongs to the larger family of molecular nuclear medicine, where trace amounts of active substances, or radiopharmaceuticals, are used to create images and to treat various diseases including cancer. SSAs are widely used in gastrointestinal NETs cancer to reduce symptoms such as diarrhoea.”

Two-Drug Combination Shows Promise Against One Type of Pancreatic Cancer

“One form of pancreatic cancer has a new enemy: a two-drug combination discovered by UF Health researchers that inhibits tumors and kills cancer cells in mouse models.

“For the first time, researchers have shown that a certain protein becomes overabundant in pancreatic neuroendocrine tumors, allowing them to thrive. They also found that pairing a  with an existing drug provides a more effective anticancer punch than a single drug. The findings were published recently in the Journal of the National Cancer Institute by a group that includes Rony A. François, an M.D./Ph.D. student working with Maria Zajac-Kaye, Ph.D., an associate professor in the UF College of Medicine’s department of anatomy and cell biology.

“Finding new treatments is critical because less than 5 percent of patients with pancreatic neuroendocrine tumors respond to everolimus, the most commonly used pharmaceutical, François said. Neuroendocrine tumors, which form in the hormone-making , account for 3 percent to 5 percent of pancreatic malignancies and have a five-year survival rate of about 42 percent, according to the National Cancer Institute. Pancreatic neuroendocrine tumors are increasingly common, which medical experts and researches have attributed to better diagnostic imaging, an aging population and heightened awareness of the disease stemming from the 2011 death of Apple Inc. co-founder Steve Jobs.”

Lexicon Pharmaceuticals Reports Positive Top-Line Results for Pivotal Phase 3 Telotristat Etiprate Study in Cancer Patients with Carcinoid Syndrome

“Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that the pivotal TELESTAR Phase 3 clinical trial met its primary endpoint, showing the benefit of oral telotristat etiprate in treating cancer patients with carcinoid syndrome that is not adequately controlled by the current standard of care. Telotristat etiprate was discovered using Lexicon’s gene science, based on Nobel Prize-winning technology, and is the company’s first discovery to complete a pivotal Phase 3 clinical trial. If approved, telotristat etiprate would be the first oral treatment successfully developed for carcinoid syndrome and the first addition to the standard of care in more than 16 years.

“Top-line results from the Phase 3 study show that patients who added telotristat etiprate to the standard of care at both the 250 mg and 500 mg doses experienced a statistically significant reduction from baseline compared to placebo in the average number of daily bowel movements over the 12-week study period (p<0.001), meeting the study’s primary endpoint.

“ ‘We are extremely pleased with these top-line results,’ said Lexicon President and Chief Executive Officer Lonnel Coats. ‘Carcinoid syndrome is severely debilitating, preventing many patients from leading active and predictable lives, and unfortunately, a majority of patients will not be adequately controlled over time with the current standard of care. We are committed to working closely with the FDA to file our first new drug application (NDA) and to bring this innovative new treatment to patients whose lives are already impacted by the challenges of cancer.’ “

Lung NETs and Their Treatment

Cancers that arise in the lung are mostly of the type known as NSCLC (non-small cell lung carcinoma). A much smaller proportion of lung tumors arise from neuroendocrine cells in the lungs. These cells (which are also found in most other organs) secrete a variety of hormones that are necessary for normal organ function, as well as for healing after injury or infection. Like other lung cells, neuroendocrine cells may transform to become cancers. Lung cancers that arise from neuroendocrine cells are called pulmonary neuroendocrine tumors (NETs), or lung NETs. Continue reading…