Everolimus improves outcomes in patients with advanced, progressive neuroendocrine tumors of gastrointestinal (GI) or unknown origin regardless of primary location and prior therapy, according to new subgroup analyses of the RADIANT-4 trial.

The phase III trial is the largest of its type in patients with nonfunctioning GI tract or lung neuroendocrine tumors. The subgroup findings for those whose tumors originated in the GI tract or an unknown site (but suspected to be GI) were presented in a presscast held in advance of the Gastrointestinal Cancers Symposium.

Compared with placebo, everolimus prolonged progression-free survival by 6-9 months, corresponding to a 46%-48% relative reduction in the risk of progression or death, reported lead study author Dr. Simron Singh of Sunnybrook’s Odette Cancer Centre in Toronto. Benefit was similar regardless of whether patients had midgut or non-midgut tumors, and whether they had previously received a somatostatin analog or not.

“In my opinion, this study in advanced, progressive neuroendocrine patients [shows] an effective, new and exciting treatment option in a disease where we’ve had very few treatments to date,” Dr. Singh said ahead of the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.

ASCO expert and presscast moderator Dr. Smitha Krishnamurthi of Case Western Reserve University, Cleveland, agreed, saying that everolimus could help address an unmet need in this disease.

“Patients with GI neuroendocrine tumors have had very few treatment options. Once they have progressed on somatostatin analogues, there really are no good systemic treatments,” she said. “So this finding is very important, that the mTOR inhibitor everolimus has demonstrated an improvement in risk of progression by over 40% and with very little severe toxicity. This is a welcome finding for these patients who have limited systemic treatment options.”

Patients enrolled in RADIANT-4 had lung, GI, or unknown-origin neuroendocrine tumors that had progressed on other therapies, including somatostatin analogs, surgery, or chemotherapy.

They were randomly assigned in 2:1 ratio to receive everolimus (Afinitor) or placebo, each in addition to best supportive care. Everolimus is currently approved by the Food and Drug Administration for the treatment of pancreatic neuroendocrine tumors, as well as breast and kidney cancer, and subependymal giant cell astrocytoma.

Results for the entire trial population have been previously reported and showed that everolimus prolonged progression-free survival by 7.1 months, reducing the risk of events by 52% (Lancet. 2015 Dec 15.[15]01234-9).

The new subgroup analyses were restricted to the patients with tumors originating in the GI tract (n =175) or an unknown site generally thought to be the GI tract (n = 36).

Among the group with GI tumors, median progression-free survival was 13.1 months with everolimus versus 5.4 months with placebo, Dr. Singh reported. Among the group with tumors of unknown origin, it was 13.6 and 7.5 months, respectively.

Relative to placebo, everolimus prolonged progression-free survival by 6.41 months, reducing the risk of events by 29%, in patients whose tumors originated in the midgut (duodenum, ileum, jejunum, cecum, or appendix). The relative benefit was 6.17 months, with a reduction in the risk of events of 73%, in patients whose tumors originated in non-midgut sites (stomach, colon, and rectum).

In addition, everolimus prolonged progression-free survival by 6.73 months, reducing the risk of events by 46%, in patients who had previously received somatostatin analogues, and by 9.07 months, reducing the risk by 48%, in patients who had not received these agents.

The safety profile of everolimus was consistent with that expected based on the use of this agent in other patient populations, according to Dr. Singh. The most common adverse events were stomatitis, infections, diarrhea, peripheral edema, and fatigue. No new safety signals were seen.

Dr. Singh disclosed that he receives honoraria from, has a consulting or advisory role with, and receives research funding (institutional) and travel, accommodations, and expenses from Novartis. The study received funding from Novartis Pharmaceuticals.