Expert Discusses Emerging Treatments, Immunotherapy Potential in pNETs

“Several recent studies have shown promise for the treatment of pancreatic NETs (pNETs). In the phase II CALGB-80701, which investigated the addition of bevacizumab (Avastin) to a treatment paradigm of everolimus and octreotide (Sandostatin) LAR in patients with locally advanced or metastatic pNETs, bevacizumab extended progression-free survival (PFS) by more than 3 months compared with everolimus and octreotide LAR alone.

“Response rate was also higher in the bevacizumab arm, with a 31% response to everolimus plus bevacizumab versus a 12% response in the control arm. Toxicity, however, was significantly higher in the bevacizumab arm.”


Video: Efficacy of Lanreotide for the Treatment of Neuroendocrine Tumors

“Martyn E. Caplin, professor, lead clinician, Neuroendocrine Unit at the Royal Free Hospital, London, discusses the efficacy of lanreotide for the treatment of patients with neuroendocrine tumors, as shown in clinical trials such as the CLARINET study.”

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Full Surgical Resection Should Be Performed Whenever Possible for Gastroenteropancreatic NETs

“Full surgical resection (R0) of gastroenteropancreatic neuroendocrine tumors (NETs) is associated with a greater than 90% survival rate at five years, according to findings presented at the 2015 North American Neuroendocrine Tumor Society (NANETS) symposium. The rate of recurrence varied by tumor location and stage, but the majority of patients with all types of NETs who underwent full resection were still free of recurrence in the five-year time frame.

“ ‘The presence of metastatic disease does not seem as though it should deter attempts at R0 resection when it’s feasible,’ according to lead author Katherine Van Loon, MD, MPH, a gastrointestinal cancer specialist at the University of California, San Francisco, Medical Center. She noted that there were differences in disease-free survival in patients who had NETs in the pancreas and small bowel depending on their stage at diagnosis, but a significant difference in overall survival was not detected.

“Current NCCN guidelines recommend that patients with gastrointestinal NETs undergo complete resection of the primary tumor and metastases whenever possible, but until now, large multicenter studies looking at recurrence rates in patients who undergo this procedure have not be conducted.”


Biomarker Needed for CAPTEM Regimen in Metastatic Pancreatic NETs

“Treatment with capecitabine and temozolomide (CAPTEM) is an effective therapy for patients with metastatic pancreatic neuroendocrine tumors (pNETs), but the efficacy of several predictive markers previously thought to determine which patients might respond to the regimen could not be validated, according to a presentation at the 2015 NANETS Symposium.

“ ‘In our study we tried to assess the role of potential predictors of response to temozolomide-based regimens in metastatic pNETs,’ according to lead author Mauro Cives, MD, who presented the findings at the 2015 North American Neuroendocrine Tumor Society symposium. The markers the investigators evaluated were expression of MGMT, proliferative activity, and ALT activation.

“Investigators looked at 143 patients with metastatic pNETs treated at Moffitt who had undergone therapy with CAPTEM and retrospectively evaluated them for radiographic response. ‘This is the largest reported cohort of pNET patients treated with temozolomide-based chemotherapy,’ said Cives, a research associate in the Department of GI Oncology at the Moffitt Cancer Center and Research Institute in Tampa, Florida.”


Video: Dr. Kunz on Potential of Immunotherapy in Neuroendocrine Tumors

“Pamela L. Kunz, MD, assistant professor of Medicine (Oncology), Stanford University School of Medicine, discusses the potential of immunotherapy in the treatment of patients with neuroendocrine tumors (NETs).

“There are currently some clinical trials under development looking at immunotherapy in NETs both at Stanford University School of Medicine and University of Pennsylvania, Kunz explains. One phase I/II trial will examine the safety and efficacy of intratumoral injection of ipilimumab combined with an anti—PD-L1 agent in these patients.”

“It is possible that immunotherapy agents could be agnostic to disease sites, Kunz says. Though it was originally believed that PD-1/PD-L1 expression is a requirement to be a predictive biomarker, additional research could show that it may not be necessary.”

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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…