Alternative dosing of exemestane in postmenopausal women with ER-positive breast cancer. Design and methods of a randomized presurgical trial

Author(s): Guerrieri-Gonzaga, Aliana; Serrano, Davide; Thomas, Parjhitham; Crew, Katherine D; Kumar, Nagi B; Gandini, Sara; Vornik, Lana A; Lee, Jack; Cagnacci, Sara; Vicini, Elisa; Accornero, Chiara A; D'Amico, Mauro; Guasone, Flavio; Spinaci, Stefano; Webber, Tania B; Brown, Powel H; Szabo, Eva; Heckman-Stoddard, Brandy; Bonanni, Bernardo | Abstract: IntroductionAromatase inhibitors are effective in lowering breast cancer incidence among postmenopausal women, but adverse events represent a barrier to their acceptability and adherence as a preventive treatment. This study aims to assess whether lowering exemestane schedule may retain biological activity while improving tolerability in breast cancer patients.Methods/designWe are conducting a, pre-surgical, non-inferiority phase IIb study in postmenopausal women with newly diagnosed estrogen receptor-positive breast cancer. Participants are randomized to receive either exemestane 25nmg/day or 25nmg/three times-week or once a week for 4 to 6nweeks prior to surgery. The primary endpoint is the percentage change of serum estradiol concentration between baseline and surgery comparing the three arms. Sample size of 180 women was calculated assuming a 6% non-inferiority of the percent change of estradiol in the lower dose arms compared with the 80% decrease predicted in the full dose arm, with 80% power and using a one-sided 5% significance level and a two-sample t-test. Main secondary outcomes are: safety; change in Ki-67 in cancer and adjacent pre-cancer tissue, circulating sex hormones, adipokines, lipid profile, insulin and glucose changes, in correlation with drug and metabolites concentrations.Results and discussionThe present paper is focused on methodology and operational aspects of the study. A total of 180 participants have ben enrolled. The trial is still blinded, and the analyses are ongoing. Despite the short term duration, results may have relevant implications for clinical management of women at increased risk of developing a ER positive breast cancer.