HER2CLIMB-05: Tucatinib Maintenance in HER2-Positive Metastatic Breast Cancer
For healthcare professionals. Educational summary of published literature; not patient-specific medical advice. Always consult the original publication.
- Study / trial name
- HER2CLIMB-05; NCT05132582
- Population
- Adults with unresectable locally advanced or metastatic HER2-positive breast cancer, randomized at the point of maintenance therapy following induction treatment
- Intervention vs. control
- Tucatinib + trastuzumab + pertuzumab vs. placebo + trastuzumab + pertuzumab, as maintenance therapy (randomized, double-blind; n=654)
- Primary endpoint & results
- Progression-free survival (investigator-assessed, RECIST v1.1). Median PFS 24.9 months (95% CI 21.3–not reached) with tucatinib vs. 16.3 months (95% CI 12.6–18.7) with placebo — a median difference of 8.6 months. HR 0.64 (95% CI 0.51–0.80; p<0.0001).
- Key secondary endpoints
- Overall survival was a secondary endpoint; OS data were not mature at the time of the primary PFS analysis.
- Toxicity
- Boxed warning for hepatotoxicity. Additional warnings/precautions: diarrhea, embryo-fetal toxicity, and increased serum creatinine without affecting renal function (per the FDA label). Specific grade ≥3 adverse-event rates were not captured in the sources reviewed for this entry.
- Practice impact
- Moves tucatinib earlier in the HER2-positive metastatic treatment course — as maintenance after induction trastuzumab/pertuzumab/taxane, rather than only after progression on prior anti-HER2 therapy (its prior approved use). FDA approved this maintenance indication on October 7, 2026.
Sources
Primary publication: Dieras V, Curigliano G, Martin M, et al. "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." J Clin Oncol. 2026;44(17):1597-1607. DOI: 10.1200/JCO-25-02600.
Regulatory source: FDA approval notice, October 7, 2026. Trial registry: ClinicalTrials.gov NCT05132582 (Phase 3).
Last reviewed: October 12, 2026
Medical guidance changes; check the latest official recommendations.
Summary written by Dr. Zubair Ali. Independent summary; not affiliated with or endorsed by the trial investigators, JCO, or FDA.