Department of Medical Oncology and State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
The Fourth Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, PR China.
Eur J Cancer. 2023 May;184:73-82. doi: 10.1016/j.ejca.2023.02.007. Epub 2023 Feb 15.
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.
比较依西美坦和氟维司群作为绝经后中国女性先前接受辅助非甾体芳香化酶抑制剂治疗≥2 年的雌激素受体阳性（ER+）/人表皮生长因子受体 2（HER2）-乳腺癌（ER+/HER2- ABC）患者的一线单药治疗的疗效。
在这项随机、开放标签、多中心、平行对照的 2 期 FRIEND 研究中，145 名绝经后 ER+/HER2- ABC 患者被分配至氟维司群（第 0、14 和 28 天给予 500mg，然后每 28±3 天给予一次，n=77）和依西美坦（25mg/天，n=67）组。主要终点是无进展生存期（PFS），次要终点是疾病控制率、客观缓解率、治疗失败时间、缓解持续时间和总生存期。探索性终点包括基因突变相关结局和安全性。
氟维司群组中位 PFS 时间（8.5 个月比 5.6 个月，p=0.014，HR=0.62，95%置信区间：0.42-0.91）、客观缓解率（19.5%比 6.0%，p=0.017）和治疗失败时间（8.4 个月比 5.5 个月，p=0.008）均优于依西美坦组。两组不良反应或严重不良反应的发生率几乎相同。在 129 名分析患者中最常见的突变发生在雌激素受体基因 1（ESR1）（18/14.0%）、PIK3CA（40/31.0%）和 TP53（29/22.5%）基因中。与依西美坦相比，氟维司群显著延长了 PFS 时间，但仅对 ESR1 野生型患者（8.5 个月比 5.8 个月）（p=0.035）有效，尽管对于 ESR1 突变患者也有类似趋势，但无统计学意义。所有 c-MYC 和 BRCA2 突变患者在氟维司群组的 PFS 时间均长于依西美坦组（p=0.049，p=0.039）。
氟维司群显著提高了 ER+/HER2- ABC 患者的总体 PFS，且耐受性良好。
NCT02646735，https://clinicaltrials.gov/ct2/show/NCT02646735。
