Everolimus delays progression of neuroendocrine tumors

Issue: February 25, 2016

Everolimus appeared to delay the progression of neuroendocrine tumors that originate in the gastrointestinal tract or are of unknown origin, according to results of a subgroup analysis of the RADIANT-4 phase 3 study presented at the Gastrointestinal Cancers Symposium.

“Everolimus has the potential to stop the cancer from growing for a prolonged period of time,” Simron Singh, MD, MPH, FRCP(C), a medical oncologist at Sunnybrook Research Institute’s Odette Cancer Center in Toronto, said in a press release. “In consultation with doctors, patients with neuroendocrine tumors may consider this as one of the new standard treatment options.”

Although neuroendocrine tumors are rare, with only approximately 8,000 diagnoses in the gastrointestinal tract each year in the U.S., their incidence is on the rise, according to a press release.

Results from the RADIANT-4 study showed everolimus (Afinitor, Novartis) significantly prolonged PFS among 302 patients with advanced, progressive nonfunctional gastrointestinal or lung neuroendocrine tumors compared with placebo (HR = 0.48; 95% CI, 0.35-0.67).

In the current subgroup analysis, researchers evaluated data from 175 patients with neuroendocrine tumors of the gastrointestinal tract — which included the stomach, colon, rectum, appendix, caecum, ileum, duodenum, jejunum or small intestine — and 36 patients with an unknown primary tumor site. Patients had been assigned 2:1 to receive 10 mg everolimus (gastrointestinal, n = 118; unknown, n = 23) or placebo (gastrointestinal, n = 57; unknown, n = 13).

The median age of patients with tumors originating in the gastrointestinal tract was 63 years and 55% of the patients were female. Researchers noted the baseline characteristics were comparable in the cohort of patients with tumors of unknown origin.

The most common tumor sites in the gastrointestinal group were the ileum (41%), the rectum (23%) and the jejunum (13%).

Patients with gastrointestinal neuroendocrine tumors achieved a PFS of 13.1 months (95% CI, 9.2-17.3) with everolimus compared to 5.4 months (95% CI, 3.6-9.3) with placebo. These data equated to a 44% reduction in risk for progression in favor of everolimus (HR = 0.56; 95% CI, 0.37-0.84).

The benefits of everolimus persisted across different patient subgroups, Singh said during a press briefing.

“In the midgut, we see very clearly there was a 29% reduction in the relative risk for progression or death and a median PFS of 6.4 months with everolimus compared to placebo,” he said. “In the non-midgut, there was a significant reduction in the relative risk for progression or death of 73% and a median PFS of 6.2 months with everolimus compared with placebo.”

Among patients with tumors of unknown origin, the median PFS for those who received everolimus was 13.6 months (95% CI, 4.1-not evaluable), compared with 7.5 months (95% CI, 1.9-18.5) for those who received placebo (HR = 0.6; 95% CI, 0.24-1.51).

Additionally, patients who had prior treatment with somatostatin analogs achieved a 46% reduction in relative risk for progression or death with everolimus, Singh said. The median PFS in this cohort was 6.7 months.

Further, treatment-naive patients treated with everolimus had a 48% reduction in the relative risk for progression or death and a median PFS of 9.1 months.

The most common serious adverse events reported in more than 5% of patients in the gastrointestinal tract subgroup, irrespective of drug–relationship, included hypertension, diarrhea, abdominal pain, stomatitis, acute renal failure and fatigue.

“This study in advanced progressive neuroendocrine cancer patients shows a new and exciting treatment option in a disease that has very few effective treatments to date,” Singh said. – by Anthony SanFilippo

Reference:

Singh S, et al. Abstract 315. Presented at: Gastrointestinal Cancers Symposium; Jan. 21-23, 2016; San Francisco.

Disclosure: This study was funded by Novartis. Singh reports consultant/advisory roles with and honoraria, research funding, and travel accommodations and expenses from Novartis. Please see the abstract for a list of all other researchers’ relevant financial disclosures.