Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial.
OBJECTIVE
To evaluate the efficacy and tolerability of fulvestrant (Faslodex; AstraZeneca Pharmaceuticals LP, Wilmington, DE), a new estrogen receptor (ER) antagonist that downregulates ER and has no agonist effects, versus tamoxifen, an antiestrogen with agonist and antagonist effects, for the treatment of advanced breast cancer in postmenopausal women.


METHODS
In this multicenter, double-blind, randomized trial, patients with metastatic/locally advanced breast cancer previously untreated for advanced disease were randomly assigned to receive either fulvestrant (250 mg, via intramuscular injection, once monthly; n = 313) or tamoxifen (20 mg, orally, once daily; n = 274). Patients' tumors were positive for ER (ER+) and/or progesterone receptor (PgR+), or had an unknown receptor status.


RESULTS
At a median follow-up of 14.5 months, there was no significant difference between fulvestrant and tamoxifen for the primary end point of time to progression (TTP; median TTP, 6.8 months and 8.3 months, respectively; hazard ratio, 1.18; 95% CI, 0.98 to 1.44; P =.088). In a prospectively planned subset analysis of patients with known ER+ and/or PgR+ tumors ( approximately 78%), median TTP was 8.2 months for fulvestrant and 8.3 months for tamoxifen (hazard ratio, 1.10; 95% CI, 0.89 to 1.36; P =.39). The objective response rate for the overall population was 31.6% with fulvestrant and 33.9% with tamoxifen, and 33.2% and 31.1%, respectively, in the known hormone receptor-positive subgroup. Both treatments were well tolerated.


CONCLUSIONS
In the overall population, between-group differences in efficacy end points favored tamoxifen, and statistical noninferiority of fulvestrant could not be demonstrated. However, in patients with hormone receptor-positive tumors, fulvestrant had similar efficacy to tamoxifen and was well tolerated.
Howell
Anthony
A
Christie Hospital and Holt Radium Institute, Manchester, UK. maria.parker@christie-tr.nwest.nhs.uk
Robertson
John F R
JF
Abram
Paul
P
Lichinitser
Mikhail R
MR
Elledge
Richard
R
Bajetta
Emilio
E
Watanabe
Toru
T
Morris
Charles
C
Webster
Alan
A
Dimery
Isaiah
I
Osborne
C Kent
CK
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D007273:Injections, Intramuscular; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000032:analysis / Q000096:biosynthesis; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol