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Keywords:

  • fulvestrant;
  • estrogen receptor antagonist;
  • duration of response;
  • combined analysis

Abstract

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, ≈ 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. Cancer 2003;98:229–38. © 2003 American Cancer Society.