24615500
BACKGROUND	In the BOLERO-2 trial , everolimus ( EVE ) , an inhibitor of mammalian target of rapamycin , demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane ( EXE ) in postmenopausal women with hormone receptor-positive ( HR ( + ) ) advanced breast cancer .
BACKGROUND	We report on the incidence , time course , severity , and resolution of treatment-emergent adverse events ( AEs ) as well as incidence of dose modifications during the extended follow-up of this study .
METHODS	Patients were randomized ( 2:1 ) to receive EVE 10 mg/day or placebo ( PBO ) , with open-label EXE 25 mg/day ( n = 724 ) .
METHODS	The primary end point was progression-free survival .
METHODS	Secondary end points included overall survival , objective response rate , and safety .
METHODS	Safety evaluations included recording of AEs , laboratory values , dose interruptions/adjustments , and study drug discontinuations .
RESULTS	The safety population comprised 720 patients ( EVE + EXE , 482 ; PBO + EXE , 238 ) .
RESULTS	The median follow-up was 18 months .
RESULTS	Class-effect toxicities , including stomatitis , pneumonitis , and hyperglycemia , were generally of mild or moderate severity and occurred relatively early after treatment initiation ( except pneumonitis ) ; incidence tapered off thereafter .
RESULTS	EVE dose reduction and interruption ( 360 and 705 events , respectively ) required for AE management were independent of patient age .
RESULTS	The median duration of dose interruption was 7 days .
RESULTS	Discontinuation of both study drugs because of AEs was higher with EVE + EXE ( 9 % ) versus PBO + EXE ( 3 % ) .
CONCLUSIONS	Most EVE-associated AEs occur soon after initiation of therapy , are typically of mild or moderate severity , and are generally manageable with dose reduction and interruption .
CONCLUSIONS	Discontinuation due to toxicity was uncommon .
CONCLUSIONS	Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education .
BACKGROUND	NCT00863655 .

