{"entity":{"id":"paper-her2climb-05-j-clin-oncol-2026","kind":"paper","name":"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","aka":[],"tldr":"Published report from the HER2CLIMB-05 trial registered as NCT05132582, in Journal of Clinical Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: The HER2CLIMB-05 study (ClinicalTrials.gov identifier: NCT05132582) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).\n\nMethods: Patients with centrally confirmed HER2+ MBC without evidence of progression post induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo twice a day combined with trastuzumab/pertuzumab. 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.\n\nResults: Between March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. 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. 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. OS data remain immature. 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. In the tucatinib arm, 13.5% discontinued tucatinib because of TEAEs.\n\nConclusion: 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.\n\nIndexed on Europe PMC as PubMed record 41369677 (DOI 10.1200/jco-25-02600). Its abstract cites the registry id NCT05132582, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2026","url":"https://doi.org/10.1200/jco-25-02600"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41369677/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41369677"},{"label":"ClinicalTrials.gov NCT05132582","url":"https://clinicaltrials.gov/study/NCT05132582"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["her2climb-05"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/jco-25-02600","pmid":"41369677","authors":"Dieras V, Curigliano G, Martin M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05132582 with the most citations, so it is the natural first reading for anyone following the HER2CLIMB-05 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-her2climb-05-j-clin-oncol-2026/","neighbours":{"trial":[{"id":"her2climb-05","kind":"trial","name":"HER2CLIMB-05","route":"/trials/her2climb-05/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}