Despite toxicity-necessitated dose reductions in most patients, everolimus is a promising treatment option for patients with advanced progressive pancreatic neuroendocrine tumors (pNETs), according to authors of a final safety analysis of data from the randomized, double-blind, placebo-controlled phase 3 RADIANT-3 trial (NET Abstract #C41), presented at the 7th Annual Neuroendocrine Tumors (NET) conference in Nashville, TN. The meeting was organized by the North American Neuroendocrine Tumors Society (NANETS).
“Encouraging signals” in TORC1 and TORC2 biomarker and clinical activity were observed in NET, “including prolonged stable disease in the majority of subjects and symptomatic improvement in those with refractory carcinoid syndrome,” reported lead study author James C. Yao, MD, of the University of Texas MD Anderson Cancer Center in Houston, TX, and coauthors.
The median treatment duration was 8 cycles (range 1-25), with a 6-month progression-free survival (PFS) rate of 85% (range 68%-94%), Dr. Yao and his coauthors reported.
Using RECIST 1.1 criteria, the best tumor response in 39 study participants undergoing CT imaging for restaging, included stable disease in 35/39, partial response in 3 participants, and progressive disease in 1 patient, the coauthors reported.
Previously reported findings from the trial include significantly-improved median PFS rate (11 months vs. 4.6 months, everolimus vs. placebo; P<0.001), the coauthors said.
A total of 207 patients with progressive pNET treatment-arm and received 10 mg/d everolimus; another 203 participants were randomized to the placebo control group. All participants received best supportive care. Upon disease progression, placebo-arm participants were allowed to cross over to open-label treatment with everolimus.
“The most common (>20%) [everolimus]-related adverse events were diarrhea, stomatitis and fatigue (70% each), rash (65%), nausea (43%), pruritus (39%), hyperglycemia (30%), anorexia (26%), thrombocytopenia and xerostomia [dry mouth] (22% each),” the coauthors reported.
Dose reduction (30 mg, 20 mg, or 15 mg daily) was necessary for 74% of study participants, usually during cycles 1 or 2. “Thereafter, treatment was well tolerated,” the coauthors noted.
“Although not prospectively collected, 12 of 15 (80%) [patients] with carcinoid reported marked reduction of flushing and 11/20 (49%) had reduced bowel movements,” they said. “Symptomatic improvement generally occurred early and persisted despite dose reduction.”
Yao’s coauthors included Du Lam and Ulrike Brandt, of Novartis. Novartis Oncology markets everolimus as Afinitor.