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…


FDA Grants Breakthrough Therapy Designation to Azedra for Pheochromocytoma, Paraganglioma

“The FDA granted breakthrough therapy designation to Ultratrace iobenguane I-131 for the treatment of patients with iobenguane-avid metastatic or recurrent pheochromocytoma and paraganglioma, according to a press release from the drug’s manufacturer.

“Ultratrace iobenguane I-131 (Azedra, Progenics Pharma), a late-state radiotherapeutic drug candidate, is being evaluated in a phase 2b trial of patients with malignant pheochromocytoma or paraganglioma. Pheochromocytomas — rare tumors usually found within one or both adrenal glands — are referred to as paragangliomas when they arise in other areas of sympathetic nerve cells.

“Ultratrace iobenguane I-131 — a very high specific activity form of iobenguane I-131 — is produced using Progenics’ Ultratrace platform, a technology designed to prevent unlabeled iobenguane from being carried through the manufacturing process to the final formulation, according to information listed on Progenics’ website. Ultratrace iobenguane I-131 is designed for use as an imaging agent in order to determine a therapeutic dose that is safe for normal organs, as well as for therapy.”


Trial Availability, Patient Eligibility Barriers to Enrollment onto Genomically Matched Trials

“Only a small percentage of patients with actionable gene alterations are eventually enrolled onto genotype-matched trials targeting these alterations, according to study results.

“With the influx of targeted molecular therapies for the treatment of cancer, genomic profiling and matching patients to targeted therapies are imperative, according to study background.

“ ‘However, implementation of genomically informed therapy requires not only access to genomic profiling, but also the availability of molecularly targeted therapies matched to the genomic testing results,’ Funda Meric-Bernstam, MD, chair of the department of investigational cancer therapeutics, at The University of Texas MD Anderson Cancer Center, and colleagues wrote. ‘Availability of clinical trials may not only differ from institution to institution, but may also differ between tumor types. Enrollment onto clinical trials is also limited by trial eligibility criteria, as well as availability of slots.’ ”


Hormone-Mimicking Drugs Are Used To Treat Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)


Neuroendocrine tumors (NETs) can arise wherever neuroendocrine (hormone-producing) cells are found—which is in most organs. Most NETs (65%-70%) are gastroenteropancreatic, or GEP, arising in different gastrointestinal organs. GEP-NETs are most commonly found in the small bowel (including the appendix), stomach, and rectum. Still, NETs in general are rare, which complicates the development of new treatments and identification of the genetic drivers of these cancers. Treatment of GEP-NETs is clearly an unmet medical need, and is now even more urgent because their incidence has been on the rise in the last 20 years. Continue reading…


Molecular Tumor Markers Could Reveal New Therapeutic Targets for Lung Cancer Treatment

The gist: New research looking into tumor mutations in small cell lung cancer (SCLC) and neuroendocrine tumors (NET) may open up new drug options to treat these conditions. Drugs called targeted therapies have been developed to treat people with tumors that have certain genetic mutations. Several targeted therapies are available for people with non-small cell lung cancer (NSCLC). But so far, targeted therapies have not been very useful in SCLC. Now, researchers have found that some SCLC and NET tumors may share some tumor mutations with NSCLC tumors. Theoretically, a patient with SCLC or NET could ask their oncologist for molecular testing to see whether their tumor(s) could potentially be treated off-label with an existing NSCLC drug. To learn more about SCLC treatment, see our Need to Know blog.

“Analysis of 607 small cell lung cancer (SCLC) lung tumors and neuroendocrine tumors (NET) identified common molecular markers among both groups that could reveal new therapeutic targets for patients with similar types of lung cancer, according to research presented today at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology. The Symposium is sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), the International Association for the Study of Lung Cancer (IASLC) and The University of Chicago Medicine.

“This study examined the clinical specimens of 607 total cases of SCLC tumors (375) and lung NET (232), which included carcinoid, atypical carcinoid and large-cell neuroendocrine tumors. Biomarker testing was achieved through a combination of DNA sequencing (Next-Generation Sequencing (NGS) or Sanger-based); immunohistochemistry (IHC) to identify which proteins are present; and in situ hybridization (ISH) testing, a form of gene amplification, to determine if any of the markers that can cause cancer cells to grow or to become resistant to treatment are present…

” ‘Even cancers that appear to be very similar can be dramatically different at the molecular level, and these differences may reflect unique vulnerabilities that could positively impact therapeutic options and decisions,’ said Stephen V. Liu, MD, senior study author and Assistant Professor of Medicine in the Division of Hematology/Oncology at Georgetown University’s Lombardi Comprehensive Cancer Center in Washington, DC. ‘We are pleased that this research confirms these rarer subtypes; it calls for additional investigation on a larger scale. Once confirmed, molecular profiling of small cell tumors and NET could become standard, as it is currently for non-small cell lung cancers, which will be especially important as more molecularly targeted chemotherapy agents are developed.’ “


FDA Grants Priority Review to Lanreotide Injection for Gastroenteropancreatic Neuroendocrine Tumors

Editor’s note: In the U.S., a drug must be approved by the U.S. Food and Drug Administration (FDA) in order for it to be prescribed to patients with specific diseases. Particularly promising drugs might be granted Priority Review, meaning that the FDA agrees to work with the drug manufacturer to accelerate the approval process. The FDA recently granted priority review to a drug meant to treat a subset of pancreatic cancer tumors known as gastroenteropancreatic neuroendocrine tumors. The drug is called lanreotide (aka Somatuline Depot). The FDA’s decision was based on promising results for the lanreotide in a clinical trial that tested it in volunteer patients.

“The U.S. Food and Drug Administration (FDA) has accepted and granted priority review to Ipsen’s supplemental New Drug Application (sNDA) for the somatostatin analog lanreotide (Somatuline Depot) 120 mg injection in the treatment of gastroenteropancreatic neuroendocrine tumors. The FDA designates priority review status to drug candidates that have the potential to offer a significant improvement in treatment compared to currently approved options. A decision is expected in early 2015.

“In the United States, lanreotide is indicated for the long-term treatment of patients with acromegaly who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy. The active substance in the drug is lanreotide acetate, a somatostatin analog that inhibits the secretion of several endocrine, exocrine, and paracrine amines and peptides.

“ ‘[Lanreotide] is the first and only somatostatin analog to demonstrate a statistically significant improvement in progression-free survival in patients with gastroenteropancreatic neuroendocrine tumors in a large, multinational clinical trial,’ said Cynthia Schwalm, President and CEO of Ipsen North America.”