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.”


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.”


Pancreatic Neuroendocrine Tumors: A Lesser Threat than Adenocarcinomas, but Still Hard to Treat


Pancreatic neuroendocrine tumors (PNETs) constitute only about 3% to 5% of all pancreatic cancers. Compared to the most common pancreatic cancer—adenocarcinoma (aka exocrine tumors), PNETs have a longer disease course and better prognosis; the 5-year survival rate is 42% for PNETs, but only about 5% to 6% for adenocarcinomas. When PNETs are localized, they can usually be removed by surgery. However, PNETs tend to metastasize, most often to the liver, and present a formidable treatment challenge at this stage. Continue reading…


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…


OncoBriefs: Local Tx for mRCC, Cervical Ca Prevention (CME/CE)

Editor’s note: This article describes three separate new findings in cancer research. The first is relevant for people with metastatic renal cell carcinoma (mRCC). Researchers have found that image-guided local ablation of tumors still has an important treatment role, even though there have been recent improvements in mRCC drugs. The second finding concerns people with metastatic neuroendocrine tumors (NETS). A clinical trial with volunteer patients found promising results for patients treated with the new drug lanreotide (aka Somatuline). The third finding has to do with preventing cervical cancer in women at high risk for the disease. The women involved in the study had high-grade cervical intraepithelial neoplasia (CIN 2/3), and were treated with surgical removal of the squamocolumnar junction (SCJ). These women had only low-grade recurrences, suggesting that removing SCJ cells might help prevent cervical cancer.

“More than 80% of patients with metastatic renal cell carcinoma (mRCC) remained alive without disease progression 3 years after image-guided local ablation of tumors, a retrospective study showed.

“Six of 76 evaluable tumors recurred an average of 1.6 years from treatment. Local ablation represents a “relatively safe procedure with acceptable local control rates,” authors concluded in an article published in the August issue of the Journal of Urology. A summary of the article leads off this edition of OncoBriefs, which also examines a somatostatin derivative for neurendocrine tumors and a surgical approach to cervical cancer prevention.”


Neutrophil Extracellular Traps Sequester Circulating Tumor Cells and Promote Metastasis

“The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets.”


Neutrophil Extracellular Traps Sequester Circulating Tumor Cells and Promote Metastasis

“The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets.”