Everolimus improved progression-free survival by 6 to 8 months compared with placebo in patients with advanced neuroendocrine tumors of the gastrointestinal tract.
A subgroup analysis from the phase III RADIANT-4 trial found that the mTOR inhibitor everolimus improved progression-free survival by 6 to 8 months compared with placebo in patients with advanced neuroendocrine tumors (NETs) of the gastrointestinal tract. These results will be presented at the 2016 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, held January 21–23 in San Francisco (abstract 315).
“In my opinion, in advanced NET patients, everolimus is an effective and new and exciting treatment option in a disease where there are few treatments to date,” said study author Simron Singh, MD, MPH, a medical oncologist at the Sunnybrook Odette Cancer Centre in Toronto, at a presscast ahead of the meeting.
The RADIANT-4 trial randomized 302 patients with advanced, progressive NETs 2:1 to either 10 mg everolimus daily or placebo. While RADIANT-4 also included patients with disease that originated in the lungs, the current analysis included patients with NETs of the gastrointestinal tract (n = 175) as well as NETs of unknown primary origin (n = 36).
The analysis found that patients with gastrointestinal NETs had a median progression-free survival of 13.1 months in the everolimus arm compared with 5.4 months in the placebo arm, with an estimated 44% risk reduction in disease progression. The most common site of NET origin was the ileum (41% of patients) followed by the rectum (23% of patients).
In patients who had NETs with an unknown primary origin, the median progression-free survival was 13.6 months in the everolimus arm compared with 7.5 months in the placebo arm, with an estimated 40% risk reduction in progression of disease.
“What was interesting in this study is that regardless of prior treatment, patients appeared to benefit from everolimus across the board,” said Singh.
All patients had disease progression following surgery, chemotherapy, or treatment with a somatostatin analog. Seventy percent of patients with gastrointestinal-originating NETs had undergone surgery, 59% had received somatostatin, and 19% had received prior chemotherapy.
Everolimus is an oral drug currently approved by the US Food and Drug Administration for the treatment of metastatic estrogen receptor–positive breast cancer, pancreatic cancer, renal cell carcinoma, and adults and children with subependymal giant cell astrocytoma.
The most common high-grade adverse events reported in more than 5% patients in the subgroup were diarrhea, hypertension, stomatitis, abdominal pain, fatigue, and acute renal failure. The adverse event profile was consistent with prior studies of everolimus with no new safety signals uncovered.
The study was funded by Novartis Pharmaceuticals.