在转移HR+/HER2-乳腺癌患者中与他莫西芬联合使用PI3K抑制:临床和循环瘤DNA结果
Rosie A B Voorthuis1, Mafalda Oliveira2, Annelot G J van Rossum3
1Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital Amsterdam, Noord-Holland Netherlands.
概括
在转移性乳腺癌患者中,tazelisib与tamoxifen结合显示出更好的无进展生存率,但显著的毒性限制了它的益处. 循环瘤DNA分析可能有助于选择患者进行向治疗.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 转移性激素受体阳性,人体表皮生长因子受体2-阴性 (HR+/HER2-) 乳腺癌通常需要新的治疗策略.
- 以前的治疗,包括内分泌疗法和循环素依赖性激酶4/6 (CDK4/6) 抑制剂,可能导致治疗耐药性.
研究的目的:
- 为了评估选择性氨酸酸 3-激酶 (PI3K) 抑制剂taselisib的安全性和疗效,与他莫西芬结合使用.
- 探索循环瘤DNA (ctDNA) 在预测预后和治疗耐药性的作用.
主要方法:
- POSEIDON试验是一项II期,随机化,安慰剂控制的研究,涉及耐火性转移性HR+/HER2-乳腺癌患者.
- 这些患者接受了taselisib + tamoxifen或安慰剂 + tamoxifen.
- 无进展生存 (PFS) 是主要终点,用于生物标志物评估进行了ctDNA分析.
主要成果:
- 相比于安慰剂+坦莫西芬 (中位数为4.8个月与3.2个月) 的治疗,塔塞利西布+坦莫西芬组合显示改善了PFS.
- 腹是与taselisib相关的最常见的不良事件.
- 在基线时高ctDNA瘤分数与更糟糕的PFS和整体存活率 (OS) 相相关.
结论:
- 用他莫西芬抑制PI3K显示在严重预处理的转移性HR+/HER2乳腺癌中具有潜在的疗效,但存在耐受性问题.
- ctDNA分析,特别是瘤部分,可以帮助患者选择向治疗和预后.
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