A Cochrane review «Fulvestrant for hormone‐sensitive metastatic breast cancer»1 «Lee CI, Goodwin A, Wilcken N. Fulvestrant for hormone-sensitive metastatic breast cancer. Cochrane Database Syst Rev 2017;(1):CD011093. »1 included 9 studies with a total of 4514 subjects. Fulvestrant is a selective oestrogen receptor down-regulator (SERD) used in hormone-sensitive locally advanced or metastatic breast cancer in postmenopausal women. Overall results for the primary endpoint of progression-free survival (PFS), mortality, or toxicity indicated that women receiving fulvestrant did at least as well as the control groups (other endocrine therapy) «Fulvestrant versus any other endocrine therapy for hormone-sensitive advanced breast cancer »1. In the one high-quality study that tested fulvestrant at the currently approved and now standard dose of 500 mg against anastrozole, women treated with fulvestrant 500 mg did better, with a hazard ratio (HR) for time to progressio of 0.66 (95% CI 0.47 to 0.93; n=205) and a HR for overall survival of 0.70 (95% CI 0.50 to 0.98; n=205). There was no difference in PFS whether fulvestrant was used in combination with another endocrine therapy or in the first- or second-line setting, when compared to control treatments: for monotherapy HR 0.97 (95% CI 0.90 to 1.04) versus HR 0.87 (95% CI 0.77 to 0.99) for combination therapy when compared to control, and HR 0.93 (95% CI 0.84 to 1.03) in the first-line setting and HR 0.96 (95% CI 0.88 to 1.04) in the second-line setting.
| Outcome | Relative effect (95% CI) | Risk with control - Any other standard endocrine therapy | Risk with intervention - Fulvestrant (95% CI) | No of women (studies) Quality of evidence |
|---|---|---|---|---|
| Time to progression follow-up: 8.9 months (mo) to 38 mo | HR 0.95 (0.89 to 1.02) | 600 per 1000 | 581 per 1000 (558 to 607) | 4258 (9) Moderate |
| Mortality follow-up for overall survival: 8.9 mo to 38 mo | HR 0.97 (0.87 to 1.09) | 400 per 1000 | 391 per 1000 (359 to 427) | 2480 (5) High |
| Vasomotor toxicity follow-up: 8.9 mo to 38 mo | RR 1.02 (0.89 to 1.18) | 2170 per 1000 | 174 per 1000 (151 to 201) | 3544 (8) High |
| Arthralgia follow-up: 8.9 mo to 38 mo | RR 0.96 (0.86 to 1.09) | 2225 per 1000 | 216 per 1000 (193 to 245) | 3244 (7) High |
| Gynaecological toxicity follow-up: 8.9 mo to 38 mo | RR 1.22 (0.94 to 1.57) | 68 per 1000 | 83 per 1000 (64 to 107) | 2848 (6) High |
See also the breast cancer guideline of American society of oncology «Burstein HJ, Somerfield MR, Barton DL et al. Endocrine Treatment and Targeted Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: ASCO Gu»2.
A phase III trial «Robertson JFR, Shao Z, Noguchi S, et al. Erratum: Fulvestrant Versus Anastrozole in Endocrine Therapy-Naïve Women With Hormone Receptor-Positive Advanced Breast Cancer: Final Overall Survival in the P»3 assessed fulvestrant vs anastrozole in endocrine therapy-naive women with hormone receptor-positive advanced breast cancer. After the primary progress free survival analysis, data were collected on survival, serious adverse events, and health-related quality of life. At the data cutoff, 314 (68.0%) of 462 patients had died (fulvestrant, 157/230 [68.3%], anastrozole, 157/232 [67.7%]). The final overalla survival (OS) analysis demonstrated no significant difference between fulvestrant and anastrozole (medians, 44.8 and 42.7 months, respectively; HR 0.97 [95% CI 0.77 to 1.21]).