Everolimus plus octreotide LAR increases median progression-free survival over octreotide LAR alone in patients with advanced neuroendocrine tumors (NETs), according to the updated results of the RAD001 In Advanced Neuroendocrine Tumors (RADIANT-2) trial presented at the 2011 Gastrointestinal Cancers Symposium (Abstract 159).
This randomized, double-blind, placebo-controlled, multicenter phase 3 trial sought to expand the options of combination therapy for NET patients by adding an oral inhibitor of mTOR, everolimus, to the standard treatment of octreotide LAR. Researchers randomized patients to either oral everolimus 10 mg/day plus octreotide LAR 30 mg intramuscular every 28 days (n = 216) or a placebo plus octreotide LAR (n = 213). Crossover to the combination was allowed at progression.
The combination therapy reduced the risk of progression by 23% over the single-agent treatment (hazard ratio [HR], 0.77; 95% confidence interval [DI], 0.59-1.00; one-sided P = .26), with median PFS increasing from 11.3 months (95% CI, 8.44-14.9) with octreotide LAR alone to 16.4 months (94% CI, 13.67-21.19) with everolimus plus octreotide LAR. Because of the high rate of informative censoring, the corrected values show a more significant increase in PFS of 5.5 months (HR, 0.60; 95% CI, 0.44-0.84; P = .0014). Further, the benefit combination treatment was seen across all subgroups (small intestine, lung, and colon).
For the combination, the most frequent adverse events included stomatitis, rash, fatigue, and diarrhea; mostly grade 1 to 2. Stomatitis, fatigue, diarrhea, infections, and hyperglycemia were reported as grade 3 to 4 in >5% of recipients.