Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials.
BACKGROUND
Fulvestrant (ICI 182,780) is a new type of estrogen receptor (ER) antagonist that down-regulates the ER and has no known agonist effects. The authors report the prospectively planned combined analysis of data from 2 Phase III trials comparing fulvestrant 250 mg monthly (n=428) and anastrozole 1 mg daily (n=423) in postmenopausal women with advanced breast carcinoma (ABC) who previously had progressed after receiving endocrine treatment.


METHODS
The primary endpoint was time to progression (TTP). Secondary endpoints included objective response (OR), duration of response (DOR), and tolerability. The trials were designed to demonstrate superiority of fulvestrant over anastrozole. Noninferiority of fulvestrant versus anastrozole was determined using a retrospectively applied statistical test.


RESULTS
At a median follow-up of 15.1 months, approximately 83% of patients in each treatment arm had progressed. The median TTP was 5.5 months in the fulvestrant group and 4.1 months in the anastrozole group, and the OR rates were 19.2% and 16.5% for fulvestrant and anastrozole, respectively (although the difference between treatments was not statistically significant). In patients who responded, further follow-up (median, 22.1 months) was performed to obtain more complete information on DOR; the median DOR (from randomization to disease progression) in patients who responded to treatment was 16.7 months in the fulvestrant group and 13.7 months in the anastrozole group. In a statistical analysis of DOR (using all randomized patients; from the start of response to disease progression), DOR was significantly longer for patients in the fulvestrant group compared with patients in the anastrozole group. Both drugs were tolerated well; withdrawals due to drug-related adverse events were 0.9% and 1.2% in the fulvestrant group and the anastrozole group, respectively. The incidence of joint disorders was significantly lower in the fulvestrant group (P=0.0036).


CONCLUSIONS
Fulvestrant was tolerated well and was at least as effective as anastrozole in the second-line treatment of patients with ABC. This new hormonaltherapy may provide a valuable treatment option for ABC in postmenopausal women.
Robertson
John F R
JF
Department of Surgery, Nottingham City Hospital, Nottingham, United Kingdom. john.robertson@nottingham.ac.uk
Osborne
C Kent
CK
Howell
Anthony
A
Jones
Stephen E
SE
Mauriac
Louis
L
Ellis
Matthew
M
Kleeberg
Ulrich R
UR
Come
Steven E
SE
Vergote
Ignace
I
Gertler
Stan
S
Buzdar
Aman
A
Webster
Alan
A
Morris
Charles
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000556:secondary; D018450:Disease Progression; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D017698:Postmenopause; D011446:Prospective Studies; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D009570:Nitriles; D014230:Triazoles; D000077267:Fulvestrant; D000077384:Anastrozole; D004958:Estradiol