National Taiwan University Hospital, Taipei, Taiwan.
Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.
J Clin Oncol. 2024 Aug 10;42(23):2812-2821. doi: 10.1200/JCO.24.00144. Epub 2024 May 21.
A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC).
In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS).
Among 222 patients randomly assigned to ribociclib plus ET (n = 112) or combination CT (n = 110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator's judgment, and 31 (14.0%) had symptomatic nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; [95% CI, 17.4 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 0.87]; = .003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm.
First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2- ABC.
在临床上侵袭性较强的激素受体阳性、人表皮生长因子受体 2 阴性（HR+/HER2-）晚期乳腺癌（ABC）患者中，从未报告过细胞周期蛋白依赖性激酶 4/6 抑制剂联合内分泌治疗（ET）与联合化疗（CT）之间疗效的头对头比较。
在这项开放标签、多中心、随机 2 期试验中，临床上侵袭性较强的 HR+/HER2-ABC 的绝经前/围绝经期女性被随机分配至一线治疗组（1:1），接受来曲唑/阿那曲唑联合戈舍瑞林或研究者选择的联合 CT（多西他赛联合卡培他滨、紫杉醇联合吉西他滨或卡培他滨联合长春瑞滨），加用或不加用ribociclib（600mg 每日 1 次，连用 3 周，停药 1 周）。主要终点为无进展生存期（PFS）。
在随机分配至 ribociclib+ET 组（n=112）或联合 CT 组（n=110）的 222 例患者中，150 例（67.6%）有症状的内脏转移，41 例（18.5%）根据研究者的判断疾病进展迅速，31 例（14.0%）有症状的非内脏疾病。总体而言，106 例（47.7%）患者有研究者评估的内脏危象。中位随访时间为 37.0 个月。数据截止时，31.3%（ribociclib 组）和 15.5%（CT 组）的患者完成了研究治疗并过渡到试验后治疗。中位 PFS 为 21.8 个月（ribociclib+ET；[95%CI，17.4 至 26.7]）和 12.8 个月（联合 CT；[95%CI，10.1 至 18.4]）；风险比为 0.61（[95%CI，0.43 至 0.87]）；=0.003。在 ribociclib 组与 CT 组中，分别观察到 66.1%和 49.0%的患者获得了总体缓解率，中位缓解时间分别为 61.8 个月和 3.2 个月（风险比，0.76[95%CI，0.55 至 1.06]）。与 CT 组相比，ribociclib 组中观察到的症状性不良事件发生率较低。
在临床上侵袭性较强的 HR+/HER2-ABC 患者中，一线 ribociclib+ET 与联合 CT 相比，具有显著的 PFS 获益、相似的缓解率和更好的耐受性。
