Capivasertib plus paclitaxel as first-line treatment for metastatic triple-negative breast cancer: results from the randomised, global phase III CAPItello-290 trial.

patients_and_methods

Patients with previously untreated metastatic TNBC were randomised 1 : 1 to paclitaxel 80 mg/m2 [day 1, weeks 1-3 (4-week cycle)] plus capivasertib 400 mg or placebo twice daily (days 2-5, weeks 1-3).

之前未接受过治疗的转移性TNBC患者按1:1比例随机分配，接受紫杉醇80 mg/m2 [第1天，第1-3周（4周周期）] 加capivasertib 400 mg或安慰剂，每日两次（第2-5天，第1-3周）。

PIK3CA/AKT1/PTEN alterations were analysed by retrospective central molecular testing.

通过回顾性中心分子检测分析了PIK3CA/AKT1/PTEN的改变。

Dual primary endpoints were OS in the overall population and in patients with PIK3CA/AKT1/PTEN-altered tumours; investigator-assessed PFS was a key secondary endpoint.

双重主要终点是总体人群的总生存和PIK3CA/AKT1/PTEN改变的肿瘤患者的总生存；研究者评估的无进展生存期是一个关键次要终点。

Results

From July 2019 to February 2022, 812 patients were randomised; 30.7% of patients had PIK3CA/AKT1/PTEN tumour alterations.

从2019年7月至2022年2月，共有812名患者被随机分配；30.7%的患者存在PIK3CA/AKT1/PTEN肿瘤改变。

At final analysis [data cut-off (DCO) 18 March 2024], the median OS for the overall population was 17.7 and 18.0 months with capivasertib-paclitaxel and placebo-paclitaxel, respectively [hazard ratio(HR) 0.92, 95% confidence interval(CI) 0.78-1.08, P = 0.3239] and for patients with PIK3CA/AKT1/PTEN-altered tumours, it was 20.4 months in both arms (HR 1.05, 95% CI 0.77-1.43, P = 0.7602).

在最终分析[数据截止日期（DCO）2024年3月18日]时，整体人群的中位总生存期为17.7个月和18.0个月，分别对应卡瓦塞尔替布-紫杉醇组和安慰剂-紫杉醇组[Hazard Ratio (HR) 0.92, 95% 置信区间 (CI) 0.78-1.08, P = 0.3239]；而对于PIK3CA/AKT1/PTEN突变肿瘤患者，两组的中位总生存期均为20.4个月（HR 1.05, 95% 置信区间 0.77-1.43, P = 0.7602）。

At PFS DCO (25 May 2022), the median PFS in the overall population numerically favoured capivasertib-paclitaxel (5.6 versus 5.1 months placebo-paclitaxel; HR 0.72, 95% CI 0.61-0.84); this was also the case in patients with PIK3CA/AKT1/PTEN-altered tumours (7.5 versus 5.6 months placebo-paclitaxel; HR 0.70, 95% CI 0.52-0.95).

在无进展生存期数据截止日期（2022年5月25日），整体人群中，卡皮瓦塞尔替-紫杉醇的中位无进展生存期数值上优于安慰剂-紫杉醇（5.6个月对比5.1个月；风险比0.72，95%置信区间0.61-0.84）；在PIK3CA/AKT1/PTEN改变的肿瘤患者中也是如此（7.5个月对比5.6个月；风险比0.70，95%置信区间0.52-0.95）。

The most frequent adverse event(AE) of grade ≥3 was diarrhoea [12.7% versus 0.7% placebo-paclitaxel (overall population)].

最常见3级及以上的不良事件是腹泻[卡皮瓦塞尔替-紫杉醇组为12.7%，而安慰剂-紫杉醇组为0.7%（整体人群）]。

Capivasertib was discontinued due to AEs in 8.5% of patients (4.9% placebo-paclitaxel; overall population); AEs led to death in 4.2% of all patients.

由于不良事件，8.5%的患者（安慰剂-紫杉醇组为4.9%；总体人群）停用了Capivasertib；所有患者中有4.2%因不良事件导致死亡。

Conclusions

Capivasertib-paclitaxel did not meet the prespecified boundary for improving OS in either population; PFS numerically favoured the combination, especially in PIK3CA/AKT1/PTEN-altered tumours.

Capivasertib-紫杉醇未达到改善总生存期的预设界限；无进展生存期数值上更倾向于联合治疗，特别是在PIK3CA/AKT1/PTEN改变的肿瘤中。

The safety of capivasertib-paclitaxel was generally manageable and consistent with prior studies.

卡皮瓦塞尔特-紫杉醇的安全性总体上是可控的，并与先前的研究结果一致。