Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
Department of Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Clin Cancer Res. 2018 Sep 15;24(18):4380-4387. doi: 10.1158/1078-0432.CCR-18-0613. Epub 2018 May 23.
This single-arm, open-label phase II study evaluated the safety and efficacy of taselisib (GDC-0032) plus fulvestrant in postmenopausal women with locally advanced or metastatic HER2-negative, hormone receptor (HR)-positive breast cancer. Patients received 6-mg oral taselisib capsules daily plus intramuscular fulvestrant (500 mg) until disease progression or unacceptable toxicity. Tumor tissue (if available) was centrally evaluated for mutations. Adverse events (AE) were recorded using NCI-CTCAE v4.0. Tumor response was investigator-determined using RECIST v1.1. Median treatment duration was 4.6 (range: 0.9-40.5) months. All patients experienced ≥1 AE, 30 (50.0%) had grade ≥3 AEs, and 19 (31.7%) experienced 35 serious AEs. Forty-seven of 60 patients had evaluable tissue for central mutation testing [20 had mutations, 27 had no mutation detected (MND)]. In patients with baseline measurable disease, clinical activity was observed in tumors with mutations [best confirmed response rate: 38.5% (5/13; 95% CI, 13.9-68.4); clinical benefit rate (CBR): 38.5% (5/13; 95% CI, 13.9-68.4)], -MND [best confirmed response rate: 14.3% (3/21; 95% CI, 3.0-36.3); CBR: 23.8% (5/21; 95% CI, 8.2-47.2)], and unknown mutation status [best confirmed response rate: 20.0% (2/10; 95% CI, 2.5-55.6); CBR: 30.0% (3/10; 95% CI, 6.7-65.2)]. Taselisib plus fulvestrant had clinical activity irrespective of mutation status, with numerically higher objective response rate and CBR in patients with -mutated (vs. -MND) locally advanced or metastatic HER2-negative, HR-positive breast cancer. No new safety signals were reported. A confirmatory phase III trial is ongoing. .
这项单臂、开放标签的 II 期研究评估了 taselisib（GDC-0032）联合氟维司群在局部晚期或转移性 HER2 阴性、激素受体（HR）阳性乳腺癌绝经后女性中的安全性和疗效。患者每日接受 6 毫克口服 taselisib 胶囊加肌肉内氟维司群（500mg），直至疾病进展或不可接受的毒性。肿瘤组织（如适用）进行中心评估 突变。使用 NCI-CTCAE v4.0 记录不良事件（AE）。使用 RECIST v1.1 由研究者确定肿瘤反应。中位治疗持续时间为 4.6 个月（范围：0.9-40.5）。所有患者均发生≥1 次 AE，30 例（50.0%）发生≥3 级 AE，19 例（31.7%）发生 35 次严重 AE。60 例患者中有 47 例可评估组织进行中心 突变检测[20 例有突变，27 例无突变（MND）]。在基线有可测量疾病的患者中，观察到有 突变的肿瘤有临床活性[最佳确认缓解率：38.5%（13 例中有 5 例；95%CI，13.9-68.4）；临床获益率（CBR）：38.5%（13 例中有 5 例；95%CI，13.9-68.4）]，-MND[最佳确认缓解率：14.3%（21 例中有 3 例；95%CI，3.0-36.3）；CBR：23.8%（21 例中有 5 例；95%CI，8.2-47.2）]和未知 突变状态[最佳确认缓解率：20.0%（10 例中有 2 例；95%CI，2.5-55.6）；CBR：30.0%（10 例中有 3 例；95%CI，6.7-65.2）]。taselisib 加氟维司群具有临床活性，与局部晚期或转移性 HER2 阴性、HR 阳性乳腺癌患者的 -MND 相比， 突变患者（vs. -MND）的客观缓解率和 CBR更高。未报告新的安全性信号。一项确证性 III 期试验正在进行中。
