title: An open randomised trial of second-line endocrine therapy in advanced breast cancer. comparison of the aromatase inhibitors letrozole and anastrozole.
abstract: It was previously shown that letrozole (Femara) was significantly more potent than anastrozole (Arimidex) in inhibiting aromatase activity in vitro and in inhibiting total body aromatisation in patients with breast cancer. The objective of this study was to compare letrozole (2.5 mg per day) and anastrozole (1 mg per day) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with an anti-oestrogen. This randomised, multicentre and multinational open-label phase IIIb/IV study enrolled 713 patients. Treatment was for advanced breast cancer that had progressed either during anti-oestrogen therapy or within 12 months of completing that therapy. Patients had tumours that were either positive for oestrogen and/or progesterone receptors (48%) or of unknown receptor status (52%). The primary efficacy endpoint was time to progression (TTP). Secondary endpoints included objective response, duration of response, rate and duration of overall clinical benefit (responses and long-term stable disease), time to treatment failure, and overall survival, as well as general safety. There was no difference between the treatment arms in TTP; median times were the same for both treatments. Letrozole was significantly superior to anastrozole in the overall response rate (ORR) (19.1% versus 12.3%, P=0.013), including in predefined subgroups (receptor status-unknown, and soft-tissue- and viscera-dominant site of disease). There were no significant differences between the treatment arms in the rate of clinical benefit, median duration of response, duration of clinical benefit, time to treatment failure or overall survival. Both agents were well tolerated and there were no significant differences in safety. These results support previous data documenting the greater aromatase-inhibiting activity of letrozole and indicate that advanced breast cancer is more responsive to letrozole than to anastrozole as second-line endocrine therapy.
authors.affiliation: Department of Oncology, Lund University Hospital, 221 85, Lund, Sweden. carsten.rose@skane.se
authors.forename: C
authors.initials: C
authors.lastname: Rose
authors.forename: O
authors.initials: O
authors.lastname: Vtoraya
authors.forename: A
authors.initials: A
authors.lastname: Pluzanska
authors.forename: N
authors.initials: N
authors.lastname: Davidson
authors.forename: M
authors.initials: M
authors.lastname: Gershanovich
authors.forename: R
authors.initials: R
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: Johnson
authors.forename: J J
authors.initials: JJ
authors.lastname: Caicedo
authors.forename: H
authors.initials: H
authors.lastname: Gervasio
authors.forename: G
authors.initials: G
authors.lastname: Manikhas
authors.forename: F
authors.initials: F
authors.lastname: Ben Ayed
authors.forename: S
authors.initials: S
authors.lastname: Burdette-Radoux
authors.forename: H A
authors.initials: HA
authors.lastname: Chaudri-Ross
authors.forename: R
authors.initials: R
authors.lastname: Lang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D000077289:Letrozole