Department of Medical Oncology and Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Nat Med. 2021 Nov;27(11):1904-1909. doi: 10.1038/s41591-021-01562-9. Epub 2021 Nov 4.
Blockade of the cyclin-dependent kinase 4 and 6 pathway has been shown to be effective in the treatment of hormone receptor-positive advanced breast cancer (ABC). We report the interim results of DAWNA-1 ( NCT03927456 ), a double-blind, randomized, phase 3 trial of dalpiciclib (a new cyclin-dependent kinase 4 and 6 inhibitor) plus fulvestrant in hormone receptor-positive, HER2-negative ABC with disease progression after endocrine therapy. A total of 361 patients were randomized 2:1 to receive dalpiciclib plus fulvestrant or placebo plus fulvestrant. The study met the primary end point, showing significantly prolonged investigator-assessed progression-free survival with dalpiciclib plus fulvestrant versus placebo plus fulvestrant (median = 15.7, 95% confidence interval (CI) = 11.1-not reached versus 7.2, 95% CI = 5.6-9.2 months; hazard ratio = 0.42, 95% CI = 0.31-0.58; one-sided P < 0.0001 (boundary was P ≤ 0.008)). The most common grade 3 or 4 adverse events with dalpiciclib plus fulvestrant were neutropenia (84.2%) and leukopenia (62.1%). The incidence of serious adverse events was 5.8% with dalpiciclib plus fulvestrant versus 6.7% with placebo plus fulvestrant. Our findings support dalpiciclib plus fulvestrant as a new treatment option for pretreated hormone receptor-positive, HER2-negative ABC.
阻断细胞周期蛋白依赖性激酶 4 和 6 通路已被证明对激素受体阳性晚期乳腺癌（ABC）的治疗有效。我们报告了 DAWNA-1 （NCT03927456）的中期结果，这是一项双盲、随机、3 期试验，研究了 dalpiciclib（一种新的细胞周期蛋白依赖性激酶 4 和 6 抑制剂）联合氟维司群治疗激素受体阳性、HER2 阴性 ABC，这些患者在内分泌治疗后疾病进展。共有 361 名患者按 2:1 的比例随机分为接受 dalpiciclib 联合氟维司群或安慰剂联合氟维司群治疗。该研究达到了主要终点，与安慰剂联合氟维司群相比，dalpiciclib 联合氟维司群显著延长了研究者评估的无进展生存期（中位数=15.7，95%置信区间[CI] = 11.1-未达到 vs. 7.2，95%CI = 5.6-9.2 个月；风险比=0.42，95%CI = 0.31-0.58；单侧 P < 0.0001（边界为 P ≤ 0.008））。与 dalpiciclib 联合氟维司群相关的最常见的 3 级或 4 级不良事件是中性粒细胞减少症（84.2%）和白细胞减少症（62.1%）。dalpiciclib 联合氟维司群组中严重不良事件的发生率为 5.8%，安慰剂联合氟维司群组中为 6.7%。我们的研究结果支持 dalpiciclib 联合氟维司群作为一种新的治疗选择，用于预处理的激素受体阳性、HER2 阴性 ABC。
