Giredestrant plus Everolimus in Advanced Breast Cancer.

Methods

In this phase 3, open-label, randomized trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who had disease progression or recurrence after receipt of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor plus endocrine therapy.

在这项III期、开放标签、随机试验中，我们招募了ER阳性、人类表皮生长因子受体2(HER2)阴性的局部晚期或转移性乳腺癌患者，这些患者在接受细胞周期依赖性激酶4和6(CDK4/6)抑制剂加内分泌治疗后疾病进展或复发。

Patients were assigned, in a 1:1 ratio, to receive giredestrant plus everolimus (each given orally) or standard endocrine therapy (i.e., exemestane, fulvestrant, or tamoxifen) plus everolimus.

患者按1:1的比例分配，接受giredestrant加everolimus（均为口服）或标准内分泌治疗（即依西美坦、氟维司群或他莫昔芬）加everolimus。

The primary end point was investigator-assessed progression-free survival, evaluated first among patients with ESR1-mutated tumors and then in the overall trial population.

主要终点是研究者评估的无进展生存期，首先评估ESR1突变肿瘤患者，然后在整体试验人群中评估。

Results

Overall, 373 patients underwent randomization, with 183 assigned to the giredestrant-everolimus group and 190 to the standard therapy-everolimus group.

共有373名患者进行了随机分组，其中183名被分配到giredestrant-everolimus组，190名被分配到标准治疗-everolimus组。

Among 207 patients with ESR1-mutated tumors, the median progression-free survivalwas 10.0 months with giredestrant-everolimus and 5.5 months with standard therapy-everolimus (hazard ratiofor disease progression or death, 0.38; 95% confidence interval[CI], 0.27 to 0.54; P<0.001).

在207名ESR1突变肿瘤患者中，giredestrant-everolimus的中位无进展生存期为10.0个月，标准治疗-everolimus为5.5个月（疾病进展或死亡的风险比为0.38；95%置信区间[CI]，0.27至0.54；P<0.001）。

In the overall population, the median progression-free survivalwas 8.8 months with giredestrant-everolimus and 5.5 months with standard therapy-everolimus (hazard ratio, 0.56; 95% CI, 0.44 to 0.71; P<0.001).

在整体人群中，giredestrant-everolimus的中位无进展生存期为8.8个月，标准治疗-everolimus为5.5个月（风险比为0.56；95% CI，0.44至0.71；P<0.001）。

Adverse events occurred in 98.9% of patients who received giredestrant-everolimus and in 96.8% of those who received standard therapy-everolimus.

98.9%的接受giredestrant-everolimus治疗的患者和96.8%的接受标准治疗-everolimus治疗的患者发生了不良事件。

The most common adverse events were stomatitis (in 47.3% of giredestrant-everolimus recipients and 48.9% of standard therapy-everolimus recipients), diarrhea (in 26.9% and 22.6%, respectively), and anemia (in 23.6% and 21.0%).

最常见的不良事件是口腔炎（在giredestrant-everolimus接受者中有47.3%，在标准治疗-everolimus接受者中有48.9%），腹泻（分别有26.9%和22.6%），以及贫血（分别有23.6%和21.0%）。

Conclusions

An all-oral giredestrant-everolimus regimen led to significantly longer progression-free survivalthan standard endocrine therapy-everolimus among patients with ER-positive, HER2-negative advanced breast cancer who had received a CDK4/6 inhibitor previously, mainly in patients with ESR1-mutated tumors.

一种全口服的giredestrant-everolimus方案在之前接受过CDK4/6抑制剂治疗的ER阳性、HER2阴性晚期乳腺癌患者中，与标准内分泌治疗-everolimus相比，显著延长了无进展生存期，主要是在ESR1突变肿瘤患者中。

The incidenceof adverse events was similar in the two groups.

两组的不良事件发生率相似。

(Funded by Genentech; evERA Breast Cancer ClinicalTrials.gov number, NCT05306340.).

该项目由Genentech资助；evERA乳腺癌临床试验的注册号为NCT05306340。