HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer.

Methods

Patients with centrally confirmed HER2+ MBC without evidence of progression post induction therapy and no or asymptomatic brain metastases (BM) were enrolled.

在诱导治疗后无进展证据且无或无症状脑转移（BM）的中心确认的 HER2+ MBC 患者被纳入研究。

Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo twice a day combined with trastuzumab/pertuzumab.

患者按1:1的比例随机分配接受tucatinib（300毫克）或安慰剂，每天两次，与trastuzumab/pertuzumab联合使用。

The primary end point is investigator-assessed progression-free survival(PFS); secondary end points include overall survival(OS), PFS per blinded independent central review, CNS-PFS, and safety.

主要终点是研究者评估的无进展生存期（PFS）；次要终点包括总生存期（OS）、盲法独立中心审查的PFS、中枢神经系统无进展生存期（CNS-PFS）和安全性。

Results

Between March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms.

在2022年3月至2024年7月期间，654名患者被随机分配到tucatinib组（n = 326）和安慰剂组（n = 328）。

All patients were female (median age, 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor-positive, and 12.4% had presence/history of baseline BM.

所有患者均为女性（中位年龄54岁），69.3%为初发性转移性乳腺癌（MBC），52.6%为激素受体阳性，12.4%有基线脑转移（BM）的存在/病史。

In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio, 0.641 [95% CI, 0.514 to 0.799]; P < .0001; median PFS: 24.9 v 16.3 months); a PFS benefit was seen regardless of the presence/absence of BM or hormone receptor status.

在这项初步分析中，与安慰剂相比，添加曲替尼显著改善了无进展生存期（PFS）（风险比，0.641 [95% 置信区间，0.514至0.799]；P < .0001；中位PFS：24.9个月对比16.3个月）；无论是否存在脑转移（BM）或激素受体状态如何，均观察到PFS获益。

OS data remain immature.

总生存（OS）数据尚未成熟。

The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (ALT: 28.2%; AST: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3.

tucatinib组中最常见的治疗后不良事件（TEAEs）是腹泻（72.7%）、恶心（33.1%）和肝酶升高（ALT：28.2%；AST：25.8%），其中6.1%、0.9%、13.5%和7.1%分别是3级或更高级别。

In the tucatinib arm, 13.5% discontinued tucatinib because of TEAEs.

在tucatinib组中，有13.5%的患者因TEAEs而停用tucatinib。

Conclusions

Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.

在曲妥珠单抗和帕妥珠单抗的基础上添加Tucatinib显示出无新的安全信号，并改善了HER2阳性转移性乳腺癌患者的无进展生存期（PFS），可能成为这些患者的1L维持治疗选择。