KEY TAKEAWAYS
- The phase 2, open-label, single-arm TUXEDO-1 trial tests trastuzumab deruxtecan.
- HER2-positive breast cancer patients with active brain metastases were tested.
- Subjects got 5.4 mg/kg intravenous trastuzumab deruxtecan every three weeks.
- The primary objective was met with a best intracranial response rate of 73.3%
- Trastuzumab deruxtecan showed no new safety signals and global quality of life.
- HER2-positive breast cancer patients with brain metastases should consider trastuzumab deruxtecan.
Antibody-drug conjugate trastuzumab deruxtecan exhibits potent extracranial action in patients with HER2-positive, metastatic breast cancer. The TUXEDO-1 experiment was a phase 2 trial with a single arm that was prospective, open-label, and randomized. Patients enrolled had to be HER2-positive, have had prior exposure to trastuzumab or pertuzumab, have no indication for immediate local therapy, and have either newly diagnosed, untreated brain metastases or brain metastases had progressed after previous local therapy and were ≥18 years old.
Once every 3 weeks, patients were given an intravenous infusion of trastuzumab deruxtecan at a dosage of 5.4 mg per kg of body weight. The primary outcome was the percentage of patients who experienced decreased brain metastases using the response evaluation in neuro-oncology criteria.
The response rate of <26% was tested versus the alternative of 61% using a Simon two-stage design. The total number of patients who received any dose of the study drug (15) is called the “intention-to-treat” population. The primary endpoint was achieved, with two patients (13.3% of the total) achieving a complete intracranial response, nine (60%) achieving a partial intracranial response, and three (20%) achieving stable disease as the best intracranial response (95% CI, 48.1%-89.1%).
Throughout treatment, there were no unexpected safety concerns raised, and subjects maintained their baseline levels of global quality of life and cognitive function. Trastuzumab deruxtecan exhibited a high intracranial response rate in the TUXEDO-1 study (NCT04752059, EudraCT 2020-000981-41) and may be evaluated as a therapy option for patients with active brain metastases from HER2-positive breast cancer.
Source: https://pubmed.ncbi.nlm.nih.gov/35941372/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT04752059
Bartsch R, Berghoff AS, Furtner J, Marhold M, Bergen ES, Roider-Schur S, Starzer AM, Forstner H, Rottenmanner B, Dieckmann K, Bago-Horvath Z, Haslacher H, Widhalm G, Ilhan-Mutlu A, Minichsdorfer C, Fuereder T, Szekeres T, Oehler L, Gruenberger B, Singer CF, Weltermann A, Puhr R, Preusser M. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Nat Med. 2022 Sep;28(9):1840-1847. doi: 10.1038/s41591-022-01935-8. Epub 2022 Aug 8. PMID: 35941372; PMCID: PMC9499862.
