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.

已显示阻断细胞周期蛋白依赖性激酶 4 和 6 通路可有效治疗激素受体阳性晚期乳腺癌 (ABC)。我们报告了 DAWNA-1 (NCT03927456) 的中期结果，这是一项 dalpiciclib（一种新的细胞周期蛋白依赖性激酶 4 和 6 抑制剂）加氟维司群治疗激素受体阳性、HER2 阴性 ABC 的双盲、随机、3 期试验内分泌治疗后疾病进展。共有 361 名患者按 2:1 随机分配接受 dalpiciclib 加氟维司群或安慰剂加氟维司群。该研究达到了主要终点，显示 dalpiciclib 加氟维司群与安慰剂加氟维司群相比，研究者评估的无进展生存期显着延长（中位数 = 15.7，95% 置信区间 (CI) = 11.1–未达到对比 7.2，95% CI = 5.6-9.2 个月；风险比 = 0.42，95% CI = 0.31–0.58；片面P  < 0.0001（边界为 P ≤ 0.008））。dalpiciclib 加氟维司群最常见的 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 加氟维司群的严重不良事件发生率为 5.8%，而安慰剂加氟维司群为 6.7%。我们的研究结果支持 dalpiciclib 加氟维司群作为预处理激素受体阳性、 HER2 阴性 ABC 的新治疗选择。