Clinical efficacy of fulvestrant versus exemestane as first-line therapies for Chinese postmenopausal oestrogen-receptor positive /human epidermal growth factor receptor 2 -advanced breast cancer (FRIEND study).

Aim: To compare the efficacies of exemestane and fulvestrant as first-line monotherapies for postmenopausal Chinese women having advanced oestrogen-receptor positive (ER+)/ human epidermal growth factor receptor 2 (HER2)-breast cancer (ER+/HER2- ABC) after a previous treatment for ≥2 years with an adjuvant non-steroidal aromatase inhibitor.
Methods: In this randomised, open-label, multi-centre, parallel-controlled phase 2 FRIEND study, 145 postmenopausal ER+/HER2- ABC patients were assigned into fulvestrant (500 mg on days 0, 14 and 28, and then at every 28 ± 3 days, n = 77) and exemestane (25 mg/day, n = 67) groups. The primary outcome was progression-free survival (PFS), while the secondary outcomes were disease control rate, objective response rate, time to treatment failure, duration of response and overall survival. Exploratory end-points included gene mutation-related outcomes and safety.
Results: Fulvestrant was superior to exemestane regarding median PFS times (8.5 versus 5.6 months, p = 0.014, HR = 0.62, 95% confidence intervals: 0.42-0.91), objective response rates (19.5% versus 6.0%, p = 0.017) and time to treatment failure (8.4 versus 5.5 months, p = 0.008). The incidence of adverse or serious adverse events in the two groups was virtually identical. The most frequent mutations in 129 analysed patients were detected in the oestrogen receptor gene 1 (ESR1) (18/14.0%), PIK3CA (40/31.0%) and TP53 (29/22.5%) genes. Fulvestrant produced significant longer PFS times compared to exemestane but only for patients with an ESR1-wild type (8.5 versus 5.8 months) (p = 0.035), although there was a similar trend also for the ESR1 mutation without statistical significance. All patients with c-MYC and BRCA2 mutations had longer PFS times in the fulvestrant versus the exemestane group (p = 0.049, p = 0.039).
Conclusion: Fulvestrant significantly increased overall PFS for ER+/HER2- ABC patients and was well tolerated.
Clinicaltrials: NCT02646735, https://clinicaltrials.gov/ct2/show/NCT02646735.
Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)