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)

• Published in: European journal of cancer (1990) 2023-05, Vol.184, p.73-82
• Main Authors: Wang, Jiayu, Cai, Li, Song, Yanqiu, Sun, Tao, Tong, Zhongsheng, Teng, Yuee, Li, Huiping, Ouyang, Quchang, Chen, Qianjun, Cui, Shude, Yin, Yongmei, Liao, Ning, Sun, Qiang, Feng, Jifeng, Wang, Xiaojia, Xu, Binghe
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; East Asian People; Estrogens - therapeutic use; Exemestane; Female; Fulvestrant; Fulvestrant - therapeutic use; HER2-negative; Humans; Oestrogen receptor-positive; Postmenopause; Progression-Free Survival; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Recurrent breast cancer (BC)
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2023.02.007

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. 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. 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). Fulvestrant significantly increased overall PFS for ER+/HER2- ABC patients and was well tolerated. NCT02646735, https://clinicaltrials.gov/ct2/show/NCT02646735. •The novel selective oestrogen receptor down regulator fulvestrant is administered to hormone receptor positive advanced breast cancer patients.•Exemestane, a steroidal aromatase inhibitors , is used to treat early and advanced breast cancer patients.•Fulvestrant was superior to exemestane regarding median progression-free survival times and time to treatment failure.•c-MYC and BRCA2 mutations led to longer progression-free survival times in the fulvestrant group.