Fulvestrant in the treatment of luminal metastatic breast cancer: the balance of effectiveness and safety

The review presents the results of studies of fulvestrant in metastatic breast cancer (MBC). Hormone therapy is an effective method of treating hormone-positive metastatic breast cancer even in the presence of visceral metastases in the absence of a visceral crisis and without detected resistance to endocrine therapy. During the COVID-19 pandemic, hormone therapy is safer for patients with hormone-positive MBC than chemotherapy, since it does not lead to immunosuppression. Fulvestrant is a “pure antiestrogen”, it has a greater affinity for estrogen receptors than tamoxifen. Fulvestrant is both a competitive antagonist and a selective estrogen receptor degrader (SERD), this mechanism of action provides complete blocking of the estrogen signaling pathway. In the phase III CONFIRM study, the optimal dose of fulvestrate was determined to be 500 mg once every 28 days, with a loading dose of 500 mg on day 15 of the first month of therapy. In the FALCON phase III study (n = 462), which included postmenopausal MBC patients who had not previously received any endocrine therapy, fulvestrant 500 mg was compared with the aromatase inhibitor anastrozole. Significant improvement in PFS was achieved with fulvestrant therapy compared to anastrozole: 16.6 months in the fulvestrant group versus 13.8 months with anastrozole [OR = 0.797; 95% CI 0.637–0.999; p = 0.0486]. A subgroup analysis showed that patients without visceral metastases can benefit most from taking fulvestrant. In all studies fulvestrant 500 mg has demonstrated a good toxicity profile, so it is being studied as a component of combined endocrine therapy. In the PALOMA-3 study the combination of fulvestrant with palbociclib (CDK4/6 inhibitor) demonstrated a median PFS 9.5 months, compared with monotherapy with fulvestrant – 4.6 months (HR = 0.46, p < 0.0001). In the MONALEESA-3 study, the median PFS in patients receiving ribociclib with fulvestrant was significantly higher compared to those taking placebo with fulvestrant: 20.5 months and 12.8 months, respectively (HR = 0.593; 95% CI: 0.480–0.732; p < 0.001). In the MONARCH-2 study the combination of fulvestrant and abemaciclib was studied in the second line of therapy, the median PFS was 16.4 months in the group of fulvestrant and abemaciclib, and 9.3 months in the group of fulvestrant and placebo (HR = 0.553; 95% CI 0.449-0.681; p < 0.0001). Fulvestrant has a satisfactory toxicity profile, does not require supporting therapy, and is included in the clinical recommendations for monotherapy and combination therapy