Tucatinib and trastuzumab emtansine for patients with previously treated HER2-positive locally advanced and metastatic breast cancer: primary analysis of the randomized phase III trial HER2CLIMB-02.

Here, we report the efficacy and safety of tucatinib in combination with T-DM1 compared with T-DM1 alone from the phase III HER2CLIMB-02 study (NCT03975647).

在此，我们报告了从III期HER2CLIMB-02研究（NCT03975647）中，曲妥珠单抗联合T-DM1与单用T-DM1相比的有效性和安全性。

patients_and_methods

Eligible patients had HER2-positive LA/MBC that had been previously treated with trastuzumab and a taxane in any setting; these included patients with brain metastases (BMs).

符合条件的患者患有HER2阳性的局部晚期/转移性乳腺癌（LA/MBC），之前已经接受过曲妥珠单抗和紫杉烷类药物治疗，无论是在何种情况下；这包括了有脑转移（BMs）的患者。

Patients were randomly assigned 1 : 1 to receive T-DM1 (3.6 mg/kg intravenously every 21 days) combined with either tucatinib (300 mg orally twice daily) in the tucatinib arm or placebo (orally twice daily) in the control arm.

患者按1:1的比例随机分配接受T-DM1（每21天静脉注射3.6 mg/kg）联合使用tucatinib（每天两次，每次300 mg口服）在tucatinib组或安慰剂（每天两次，口服）在对照组。

Results

In total, 463 patients were randomly assigned.

共有463名患者被随机分配。

After a median follow-up duration of 24.4 months, the median progression-free survival(PFS) was 9.5 months in the tucatinib arm and 7.4 months in the control arm [hazard ratio(HR) 0.76, 95% confidence interval(CI) 0.61-0.95, P = 0.0163].

经过中位随访时间24.4个月后，tucatinib组的中位无进展生存期（PFS）为9.5个月，对照组为7.4个月[风险比（HR）0.76，95%置信区间（CI）0.61-0.95，P = 0.0163]。

A PFS benefit was observed across all prespecified subgroups, including in patients with BMs.

在所有预先设定的亚组中观察到无进展生存（PFS）的获益，包括脑转移（BMs）患者。

Interim overall survivalanalysis results were immature.

中期总生存（OS）分析结果尚不成熟。

The median OS was not reached in the tucatinib arm and was 38.0 months in the control arm (HR 1.23, 95% CI 0.87-1.74).

在 tucatinib 组中，中位总生存期尚未达到，在对照组中为 38.0 个月（风险比 HR 1.23，95% 置信区间 CI 0.87-1.74）。

The incidences of treatment-emergent adverse events (TEAEs) associated with any treatment discontinuation and of grade ≥3 TEAEs were higher in the tucatinib arm than in the control arm (22.1% versus 11.6% and 68.8% versus 41.2%, respectively).

与任何治疗中断相关的治疗后不良事件（TEAEs）的发生率以及≥3级 TEAEs 的发生率在 tucatinib 组中高于对照组（分别为 22.1% 对比 11.6% 和 68.8% 对比 41.2%）。

The most common grade ≥3 TEAEs in the tucatinib arm were elevated alanine aminotransferase (16.5%) and aspartate aminotransferase levels (16.5%) (versus 2.6% for both in the control arm).

在tucatinib组中，最常见的3级或更高级别的不良事件是丙氨酸氨基转移酶升高（16.5%）和天冬氨酸氨基转移酶水平升高（16.5%）（对照组中两者均为2.6%）。

Conclusions

The addition of tucatinib to T-DM1 improved PFS in patients with previously treated HER2-positive LA/MBC, including patients with BMs, and exhibited a manageable safety profile.

将tucatinib添加到T-DM1中，改善了既往接受治疗的HER2阳性LA/MBC患者的无进展生存期（PFS），包括有脑转移的患者，并展示了可管理的安全性特征。