Dr Hamilton on First-Line Tucatinib-Based Maintenance in HER2+ Metastatic Breast Cancer

“In terms of efficacy, HER2CLIMB-05 met its primary end point, which was progression-free survival [PFS]. By investigator assessment, PFS was lengthened by 8.6 months [with tucatinib plus trastuzumab and pertuzumab vs placebo plus trastuzumab and pertuzumab].”

Erika P. Hamilton, MD, director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute, discussed efficacy results from the phase 3 HER2CLIMB-05 trial (NCT05132582), a randomized, double-blind study evaluating tucatinib (Tukysa) in combination with trastuzumab (Herceptin) and pertuzumab (Perjeta) vs placebo plus trastuzumab and pertuzumab as first-line maintenance therapy for patients with HER2-positive metastatic breast cancer following induction chemotherapy.

HER2CLIMB-05 met its primary end point of investigator-assessed progression-free survival (PFS), demonstrating a statistically significant and clinically meaningful improvement with the incorporation of tucatinib, Hamilton reported, who noted that maintenance therapy with tucatinib prolonged PFS by 8.6 months compared with the placebo regimen. The median PFS was 24.9 months for patients treated with the tucatinib regimen (n = 326) vs 18.3 months for those given the placebo regimen (n = 328; HR, 0.641; 95% CI, 0.514-0.799; P < .0001). She emphasized that this magnitude of benefit—effectively lengthening disease control from 1.5 years to beyond 2 years—represents a substantial improvement in a metastatic setting, in which patients typically experience gradual attrition of therapeutic benefit over time.

Hamilton also explained that subgroup analyses demonstrated that the PFS benefit of tucatinib was consistent irrespective of hormone receptor status. She noted that these findings reinforce the broad applicability of tucatinib within HER2-positive metastatic breast cancer and highlight the importance of continued HER2-directed suppression following initial chemotherapy.

The trial’s design—maintenance therapy following standard taxane-based induction with trastuzumab and pertuzumab—mirrors contemporary frontline practice, underscoring the immediate relevance of these data to routine clinical decision-making. The observed PFS improvement, Hamilton explained, supports the strategy of intensifying HER2 blockade with a highly selective HER2-targeted TKI in tucatinib to delay disease progression and potentially improve long-term outcomes.

Hamilton concluded that HER2CLIMB-05 provides compelling evidence to support tucatinib as an effective component of maintenance therapy in the first-line HER2-positive metastatic breast cancer setting.