Background: In the phase III RADIANT-3 trial, everolimus, an oral mTOR inhibitor, demonstrated superiority in progression-free survival with a median of 11.0 vs 4.6 months for placebo (hazard ratio, 0.35; 95% confidence interval, 0.27 to 0.45; P<0.0001) in patients with advanced pNET (ESMO 2010, Abstract #LBA9). Here we present an update of the safety analysis from this trial.
Methods: Patients with progressive advanced low- or intermediate-grade pNET were randomized to everolimus 10 mg/day orally (n=207) or placebo (n=203); both arms received best supportive care. Adverse events (AEs) were collected and coded to a preferred term using the medical dictionary for regulatory activities. AEs were graded using the National Cancer Institutes Common Terminology Criteria for AEs (v 3.0). Safety population included 407 patients (204 for everolimus; 203 for placebo).
Results: Median study follow-up was 20.1 months. Safety of everolimus was consistent with the primary analysis (median follow-up 17 months). Median exposure to everolimus was 2.3-fold longer than placebo (37 vs 16 weeks), corresponding to exposures of 175.2 vs 104.9 patient-years, respectively. Most common drug-related AEs with everolimus versus placebo were stomatitis (52.9 vs 12.3%), rash (48.5 vs 10.3%), diarrhea (34.3 vs 10.3%), and fatigue (32.4 vs 14.3%). Anemia (5.9 vs 0%), hyperglycemia (5.9 vs 2.5%), stomatitis (4.9% vs 0), and thrombocytopenia (3.9 vs 0%) were the most common drug-related grade 3/4 events for everolimus and placebo, respectively. Most AEs resolved with dose modification/interruptions or concomitant medication. Rate of drug-related AEs leading to discontinuation was relatively low (13.7% everolimus versus 2.0% placebo). Disease progression remained the primary reason for discontinuation from both treatment arms.
Conclusions: Safety of everolimus in pNET patients observed in this updated analysis is consistent with previous experience and provides further evidence of the favorable risk-benefit profile of everolimus in advanced pNET patients.
Acknowledgment: Study is sponsored by Novartis.
30 Apr - 04 May 2011
European Society of Endocrinology