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 tumour growth, compared to octreotide alone.
Neuroendocrine tumours, also known as carcinoids, are uncommon tumours 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 tumours," said Doctor James C. Yao. "This research offers a promising option where there were limited options previously."
According to Yao, the number of people diagnosed with neuroendocrine tumours 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 per cent 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 tumour cell division and blood vessel growth in cancer cells. Overaction of mTOR has been implicated in the pathogenesis of neuroendocrine tumours.
The study, named RADIANT-2, enrolled 429 participants with low-grade or intermediate-grade advanced (unresectable locally advanced or distant metastatic) neuroendocrine tumours 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 per cent vs. 14 per cent), fatigue (31 per cent vs. 23 per cent) and diarrhea (27 per cent vs. 16 per cent).
MEDICA.de; Source: University of Texas MD Anderson Cancer Centre