In a subgroup analysis of the phase III RADIANT-4 trial, focusing on neuroendocrine tumors of gastrointestinal origin, the mTOR inhibitor everolimus (Afinitor) essentially doubled the median progression-free survival time, compared with placebo, researchers reported at the 2016 Gastrointestinal Cancers Symposium in San Francisco, California.1
Everolimus is approved by the U.S. Food and Drug Administration for the treatment of neuroendocrine tumors arising in the pancreas of patients with progressive disease.
The primary analysis of RADIANT-4 was presented in the fall of 2015 at the European Cancer Congress.2 At that time, researchers reported a highly significant 52% reduction in the relative risk of disease progression in the entire study population, which included patients with advanced gastrointestinal and lung neuroendocrine tumors (P < .00001).
“This was quite a stunning finding—a 7-month improvement in progression-free survival,” said
Simron Singh, MD, MPH of Sunnybrook’s Odette Cancer Centre in Toronto, Canada, who presented the subsequent analysis in San Francisco.
The subgroup analysis included 175 patients with previously treated, nonfunctional, advanced gastrointestinal neuroendocrine tumors and 36 patients with neuroendocrine tumors from an unknown site. Patients were randomized to receive everolimus at 10 mg/d or placebo until disease progression.
Overall, everolimus reduced the risk of disease progression by 40% or more, compared with placebo. By tumor type, median progression-free survival was 13.1 months vs 5.4 months for the gastrointestinal subset (hazard ratio [HR] = 0.56) and 13.6 vs 7.5 months, respectively, among patients with tumors of an unknown origin (HR = 0.60).
Everolimus and Neuroendocrine Tumors
- A subgroup analysis of RADIANT-4, focusing on neuroendocrine tumors of gastrointestinal or unknown origin, showed approximately a 40% reduction in the risk of disease progression with everolimus, vs placebo.
- Median progression-free survival was 13.1 months with everolimus vs 5.4 months with placebo, for the gastrointestinal subset, and 13.6 vs 7.5 months, respectively, among patients with tumors of unknown origin.
- The drug was beneficial in midgut and nonmidgut tumors as well as in patients naive to or previously treated with somatostatin analogs.
“This was clearly a significant improvement in stopping tumors from growing with everolimus,” Dr. Singh commented at a press briefing. “This study suggests everolimus is a new, effective, exciting treatment option.”
Midgut vs Nonmidgut Tumors
Delving deeper into the findings, the researchers showed a relative risk reduction of 29% for patients with tumors in the midgut (ileum, jejunum, cecum, duodenum, appendix, and small intestine), who had an absolute 6.4-month improvement in median progression-free survival. For patients with tumors in nonmidgut sites (stomach, colon, rectum), the risk reduction was 73%, and the absolute gain in median progression-free survival was 6.2 months, Dr. Singh reported.
The toxicity profile of everolimus is by now familiar, and there were no new safety signals, Dr. Singh said.
‘A Welcome Finding’
Smitha Krishnamurthi, MD
ASCO spokesperson Smitha Krishnamurthi, MD, of Seidman Cancer Center and the Case Comprehensive Cancer Center, Cleveland, Ohio, commented on the results of the RADIANT-4 trial. “While everolimus is already approved for treating pancreatic neuroendocrine tumors, these results demonstrate that it may also be effective for a broader group of patients. The findings are important, showing an improvement in the risk of progression by more than 40%, without severe toxicity. This is a welcome finding for patients with limited systemic treatment options.” ■
Disclosure: Dr. Singh has received honoraria, research funding, and travel expenses from as well as served as a consultant or advisor for Novartis. Dr. Krishnamurthi reported no potential conflicts of interest.
References
1. Singh S, Carnaghi C, Buzzoni R, et al: Efficacy and safety of everolimus in advanced, progressive, nonfunctional neuroendocrine tumors of the gastrointestinal tract and unknown primary: A subgroup analysis of the phase III RADIANT-4 trial. 2016 Gastrointestinal Cancers Symposium. Abstract 315. Presented January 22, 2016.
2. Yao J, Fazio N, Singh S, et al: Everolimus in advanced nonfunctional neuroendocrine tumors of lung or gastrointestinal origin: Efficacy and safety results from the placebo-controlled, double-blind, multicenter, phase III RADIANT-4 study. 2015 European Cancer Congress. Abstract LBA5. Presented September 27, 2015.
