Results of the CONFIRM Phase III Trial Comparing Fulvestrant 250 mg With Fulvestrant 500 mg in Postmenopausal Women With Estrogen Receptor–Positive Advanced Breast Cancer

Abstract

Fulvestrant 500 mg was associated with a statistically significant increase in PFS and not associated with increased toxicity, corresponding to a clinically meaningful improvement in benefit versus risk compared with fulvestrant 250 mg.

Clinical utility of fulvestrant in the treatment of breast cancer: a report on the emerging clinical evidence

“…The randomized Phase II Faslodex Investigation of Dose Evaluation in Estrogen Receptor-Positive Advanced Breast Cancer (FINDER) trials 149 and 2,50 carried out in Japanese and non-Japanese patients respectively, compared fulvestrant IAD with LD and HD in postmenopausal women with HR-positive ABC recurring or progressing after prior endocrine therapy, reporting a trend toward improved efficacy with HD and LD compared to the IAD. They set the ground for the large confirmatory Phase III study Comparison of Fulvestrant In Recurrent or Metastatic Breast Cancer (CONFIRM), comparing fulvestrant HD versus the IAD in 736 postmenopausal women with ER-positive ABC who experienced disease progression during adjuvant or first-line endocrine therapy or within 1 year from completion of adjuvant endocrine therapy, about two-thirds of whom had acquired endocrine resistance and a third had primary resistance 65. PFS was significantly longer with the HD compared to the IAD (hazard ratio 0.80, 95% CI 0.68–0.94; P =0.006).…”

“…The CONFIRM study65 reported the following grade 1–4 AEs with fulvestrant HD: gastrointestinal 20.2%, joint disorders 18.8%, injection-site reactions 13.6%, hot flashes 8.3%, urinary tract infection 2.2%, ischemic cardiovascular disorders 1.4%, thromboembolic events 0.8%, vaginitis 0.8%, osteoporosis 0.3%, and weight gain 0.3%. Grade ≥3 AEs were gastrointestinal disturbances 2.2%, joint disorders 2.2%, thromboembolic events 0.6%, injection-site reactions 0.3%, and urinary tract infection 0.3%.…”

“…On the other hand, in PALOMA-3, adding palbociclib to fulvestrant significantly delayed the deterioration of global QoL and pain 110. In the CONFIRM trial, no differences were found in TOI scores between the two fulvestrant dosages 65. Treatment compliance with fulvestrant may be supported by its monthly IM administration, often provided at outpatient clinics, although patient preference for IM compared with oral administration has not been assessed and could change from patient to patient and over time.…”

AGO Recommendations for the Diagnosis and Treatment of Patients with Advanced and Metastatic Breast Cancer: Update 2014

“…If the cancer progressed on therapy with non-steroidal AI (letrozole or anastrozole) or if an AI therapy was terminated less than 1 year ago, two distinct options for endocrine treatment may be considered, i.e. (i) fulvestrant (500 mg every 4 weeks) [9] or (ii) a combination of exemestane plus everolimus [10] (fig. 2).…”

Low-Dose Fulvestrant Maintained Long-Term Complete Remission after Poor Response to Previous Endocrine Therapies in a Patient with Advanced Breast Cancer

“…The neoadjuvant NEWEST trial [6] showed significantly greater biological activity benefit with high-dose fulvestrant compared to the approved dose. The randomized, double-blind CONFIRM (Comparison of Faslodex in Recurrent or Metastatic Breast Cancer) trial presented recently [7] has shown a small but statistically significant increase in time to progression for fulvestrant 500 mg compared with fulvestrant 250 mg, without increase of toxicity.…”