Everolimus prolongs progression-free survival for patients with neuroendocrine tumors

November 29, 2011

HOUSTON -- Combination treatment with everolimus, an inhibitor of the mammalian target rapamycin (mTOR), and octreotide has shown to improve progression-free survival for patients with advanced neuroendocrine tumors and a history of carcinoid syndrome, according to researchers at The University of Texas MD Anderson Cancer Center.

Results of the international, randomized, placebo-controlled Phase III study were published today in the journal Lancet.

The treatment combination of everolimus and octreotide long-acting repeatable (LAR), a somatostatin analogue that has shown antitumor activity, led to a clinically meaningful five-month delay in tumor growth, compared to octreotide alone.

Neuroendocrine tumors, also known as carcinoids, are uncommon tumors arising from various primary sites. Frequently, carcinoids spread to the liver, causing a variety of symptoms termed carcinoid syndrome.

"There are currently no Food and Drug Administration (FDA) approved drugs for oncologic control of most neuroendocrine tumors," said James C. Yao, M.D., associate professor in MD Anderson's Department of Gastrointestinal Medical Oncology. "This research offers a promising option where there were limited options previously."

Dangerous and rare tumors


According to Yao, the number of people diagnosed with neuroendocrine tumors has increased more than five-fold over the past 30 years, from one in 100,000 people per year to 5.25 in 100,000 people per year. Nearly half of patients have regional or distant metastatic disease and 65 percent of those with advanced disease die within five years of diagnosis.

Everolimus, an immunosupressant agent used to prevent rejection of organ transplants, inhibits the mTOR protein, a central regulator of tumor cell division and blood vessel growth in cancer cells. Overaction of mTOR has been implicated in the pathogenesis of neuroendocrine tumors.

Preclinical studies have shown that mTOR inhibition may control growth of neuroendocrine tumors, and an earlier Phase II study at MD Anderson showed promising anti-cancer activity for everolimus in neuroendocrine tumors.

In May of this year, an international randomized Phase III study showed everolimus improved progression-free survival in pancreatic neuroendocrine tumors, a related disease, leading to its FDA approval for treatment of those rare tumors.

Somatostatin analogues, such as octreotide, improve hormone-related symptoms associated with neuroendocrine tumors. Octreotide LAR has also shown antitumor activity, prolonging time to disease progression in patients with certain types of neuroendocrine tumors.

Increase in progression-free survival

The study, named RADIANT-2, enrolled 429 participants with low-grade or intermediate-grade advanced (unresectable locally advanced or distant metastatic) neuroendocrine tumors and a history of carcinoid syndrome. Disease progression had been established by radiological assessment within the past 12 months.

Patients were given either 10 mg per day oral everolimus or placebo, both in conjunction with 30 mg intramuscular octreotide LAR, every 28 days. Treatment was continued until disease progression, withdrawal from treatment because of adverse effects or withdrawal of consent.

Median progression-free survival by was 16.4 months in the everolimus plus octreotide LAR group and 11.2 months in the placebo plus octreotide LAR group.

Side effects were higher but manageable in the combination arm. They included stomatitis (62 percent vs. 14 percent), fatigue (31 percent vs. 23 percent) and diarrhea (27 percent vs. 16 percent).

Next steps

Yao said additional exploratory analyses to adjust for the effect of randomization imbalances will be presented at American Society of Clinical Oncology (ASCO) gastrointestinal annual meeting in 2012.

"We are working with industry sponsor [Novartis] to develop a confirmatory study in neuroendocrine tumors," he said.
-end-
Researchers with Yao included Marianne Pavel, M.D., Charite-Universitatsmedizin, Berlin; John Hainsworth, M.D., Cannon Research Institute, Nashville; Eric Baudin, M.D., Oncologie Endocrinienne et Medecine Nucleaire, Villejuif, France; Marc Peeters, M.D., Antwerp University Hospital, Belgium; Dieter Horsch, M.D., Klinik fur Innere Medizin, Zenttralklinik Bad Berka GmbH, Germany; Robert Winkler, M.D., Judith Klimovsky, M.D. and David Lebwohl, M.D., Ochsner Kenner Medical Center, Louisiana; Valentine Jehl, MSc, Novartis Pharma AB, Switzerland; Edward Wolin, M.D., Ceders Sinai Medical Center, Los Angeles; Kjell Oberg, M.D., University Hospital, Uppsala, Sweden; and Eric Van Cutsem, M.D., University Hospital Gasthuisberg, Leuven, Belgium. Yao is a consultant to and has received research funding from Novartis.

University of Texas M. D. Anderson Cancer Center

Related Disease Progression Articles from Brightsurf:

SGLT2 inhibitors can slow progression of chronic kidney disease
The CREDENCE trial [3] provided evidence that the SGLT2 inhibitor Canagliflozin slows the progression of CKD in individuals with type 2 diabetes (T2D) and CKD with albuminuria.

Cardiac biomarker shows stronger associations with kidney disease progression than BP
Identifying biomarkers for kidney disease progression may elucidate disease pathways and inform treatment.

Pilot study suggests Parkinson's disease progression can be slowed
Deep Brain Stimulation (DBS) implanted in early stage Parkinson's disease decreases the risk of disease progression and the need to prescribe multiple drugs to patients simultaneously, according to a five-year outcomes study of 30 patients released in the July 2020, issue of Neurology®, the medical journal of the American Academy of Neurology.

Could the blood of COVID-19 patients be used to predict disease progression?
Researchers from Charité - Universitätsmedizin Berlin and the Francis Crick Institute have identified 27 proteins which are present at different levels in the blood of COVID-19 patients, depending on the severity of their symptoms.

Fatal cases of COVID-19 deepen our understanding of the disease's progression
Identifying risk factors underlying fatal COVID-19 cases is critical to understanding - and treating - the deadly disease.

Language disorders as indicators of the diagnosis and progression of Huntington's disease
A study led by Wolfram Hinzen, ICREA research professor with the Department of Translation and Language Sciences, published in Journal of Communication Disorders, shows that the first symptoms of the disease are revealed through linguistic changes in spontaneous speech.

Early treatment of schizophrenia may not slow disease progression
A Stony Brook University-led study reveals that, despite the common view that early intervention in schizophrenia slows or stops mental decline, those who receive early intervention eventually experience the same declines as those whose treatment started later.

Simple blood test could help predict progression of Parkinson's disease
In order to provide the best medical care for newly diagnosed Parkinson's disease (PD) patients, a method of predicting their cognitive and motor progression, beyond using purely clinical parameters, would have major implications for their management.

AI-analyzed blood test can predict the progression of neurodegenerative disease
A new study shows artificial intelligence (AI) analysis of blood samples can predict and explain disease progression, which could one day help doctors choose more appropriate and effective treatments for patients.

Discovery could help slow down progression of Parkinson's disease
A collaboration between scientists at Rutgers University and Scripps Research leads to the discovery of a small molecule that may slow down or stop the progression of Parkinson's disease

Read More: Disease Progression News and Disease Progression Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.