VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor-Positive/HER2-/PIK3CA Wild-Type Advanced Breast Cancer.

Methods

This phase III randomized trial (VIKTORIA-1; ClinicalTrials.gov identifier: NCT05501886) evaluated the efficacy of gedatolisib-based therapy, comparing gedatolisib, palbociclib, and fulvestrant (gedatolisib triplet) and gedatolisib plus fulvestrant (gedatolisib doublet) with fulvestrant monotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2-), PIK3CA wild-type (WT) advanced breast cancer.

这项 III 期随机试验（VIKTORIA-1; ClinicalTrials.gov 标识符: NCT05501886）评估了基于 gedatolisib 的治疗效果，比较了 gedatolisib、palbociclib 和 fulvestrant（gedatolisib 三联疗法）以及 gedatolisib 加 fulvestrant（gedatolisib 二联疗法）与 fulvestrant 单药治疗在激素受体阳性、人类表皮生长因子受体2阴性（HER2-）、PIK3CA 野生型（WT）晚期乳腺癌患者中的疗效。

Eligible patients had disease progression during or after CDK4/6 inhibitor and aromatase inhibitor treatment.

符合条件的患者在CDK4/6抑制剂和芳香酶抑制剂治疗期间或之后出现疾病进展。

Comparison of progression-free survivalas assessed by blinded independent central review for gedatolisib triplet versus fulvestrant and gedatolisib doublet versus fulvestrant was the primary objective.

通过盲法独立中央审查评估的无进展生存期比较，gedatolisib三联疗法与fulvestrant以及gedatolisib双联疗法与fulvestrant是主要研究目标。

Results

A total of 392 patients were randomly assigned 1:1:1.

共有392名患者按1:1:1的比例随机分配。

The median study follow-up was 10.1 months.

研究的中位随访时间为10.1个月。

The median progression-free survivalwas 9.3 months in the gedatolisib-triplet group, 2.0 months in the fulvestrant group (hazard ratio[HR] for progression or death, 0.24 [95% CI, 0.17 to 0.35]; P < .001), and 7.4 months in the gedatolisib-doublet group (HR, 0.33 [95% CI, 0.24 to 0.48]; P < .001 v fulvestrant).

在gedatolisib-triplet组中，无进展生存期的中位数为9.3个月，在fulvestrant组为2.0个月（进展或死亡的风险比[HR]为0.24 [95%置信区间, 0.17至0.35]；P < .001），在gedatolisib-doublet组为7.4个月（HR为0.33 [95%置信区间, 0.24至0.48]；与fulvestrant组相比P < .001）。

Grade ≥3 treatment-related adverse events (TRAEs) reported in the gedatolisib-triplet and gedatolisib-doublet groups, respectively, included neutropenia (62.3%, 0.8%), stomatitis (19.2%, 12.3%), rash (4.6%, 5.4%), hyperglycemia (2.3%, 2.3%), and diarrhea (1.5%, 0.8%).

在gedatolisib-triplet组和gedatolisib-doublet组中分别报告的3级或以上治疗相关不良事件（TRAEs）包括中性粒细胞减少症（62.3%，0.8%）、口腔炎（19.2%，12.3%）、皮疹（4.6%，5.4%）、高血糖（2.3%，2.3%）和腹泻（1.5%，0.8%）。

Study treatment discontinuation because of TRAEs was reported in 2.3% (triplet) and 3.1% (doublet) of patients.

因治疗相关不良事件导致研究治疗中断的情况在2.3%（三药联合组）和3.1%（两药联合组）的患者中报告。

Conclusions

The addition of gedatolisib to fulvestrant, with or without palbociclib, significantly reduced the risk of disease progression or death in patients with hormone receptor-positive/HER2-, PIK3CA WT advanced breast cancer.

在激素受体阳性/HER2阴性、PIK3CA野生型的晚期乳腺癌患者中，添加gedatolisib到fulvestrant，无论是否联合palbociclib，显著降低了疾病进展或死亡的风险。