Dr Hamilton on Tucatinib Maintenance Efficacy in HER2+ Breast Cancer

Erika Hamilton, MD, discusses updated data from the HER2CLIMB-05 trial (NCT05132582) presented at the 2026 ASCO Annual Meeting. Hamilton is the chief development officer, Late Phase; director, Breast Cancer Research, at Sarah Cannon Research Institute (SCRI).

Adding tucatinib (Tukysa) to first-line maintenance therapy with trastuzumab (Herceptin) and pertuzumab (Perjeta) produced clinically meaningful improvements in progression-free survival (PFS) and other end points in patients with HER2-positive metastatic breast cancer regardless of key disease characteristics, according to subgroup analyses from the phase 3 HER2CLIMB-05 trial presented at ASCO 2026.

Overall, median PFS improved by nearly 9 months with tucatinib plus trastuzumab/pertuzumab vs placebo plus trastuzumab/pertuzumab (24.9 vs 16.3 months; HR 0.641; P <.0001). The benefit was consistent across all prespecified subgroups, including hormone receptor (HR) status, presence or absence of brain metastases, and whether disease was de novo or recurrent.

Patients with HR-negative disease derived substantial benefit, with median PFS of 24.9 vs 12.6 months (HR, 0.554), while those with HR-positive disease also showed improvement (25.0 vs 18.1 months; HR, 0.725). Among HR-positive patients receiving endocrine therapy, median PFS reached 27.2 months with tucatinib, underscoring the importance of endocrine therapy integration in dual-positive metastatic disease.

Baseline brain metastases were uncommon, present in 12.4% of patients; tucatinib numerically doubled PFS in this group (8.5 vs 4.2 months; HR, 0.640), while patients without brain metastases achieved a 27.2-month median PFS with tucatinib.

The PFS benefit with tucatinib extended across all prespecified subgroups, including de novo versus recurrent disease, prior anti-HER2 therapy, best response to induction therapy, visceral vs nonvisceral disease, ECOG performance status, region, age, and race.

Treatment-emergent adverse events were consistent across all examined subgroups, with grade 3 or higher events occurring in 42% of patients receiving tucatinib vs 24% with placebo, and without excess discontinuations. These findings reinforce tucatinib plus trastuzumab/pertuzumab as a broadly applicable first-line maintenance option for patients with HER2-positive metastatic breast cancer.

REFERENCE

Hamilton EP, Curigliano G, Martin M, et al. Efficacy and safety of tucatinib (TUC) vs placebo (PBO) combined with trastuzumab and pertuzumab (HP) as maintenance therapy for HER2+ metastatic breast cancer by stratified subgroups. J Clin Oncol. 2026;44(suppl 16):1005. doi: 10.1200/JCO.2026.44.16_suppl.1005