Neuro-oncology · 2024
Final outcome analysis from the phase II TUXEDO-1 trial of trastuzumab-deruxtecan in HER2-positive breast cancer patients with active brain metastases.
Клиническое исследование II фазыСтатьяНазвание и аннотация: Перевод пока не подготовлен
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Bartsch Rupert, Berghoff Anna Sophie, Furtner Julia, Marhold Maximilian, Bergen Elisabeth Sophie, Roider-Schur Sophie, Mair Maximilian Johannes, Starzer Angelika Martina, Forstner Heidrun, Rottenmanner Beate, Aretin Marie-Bernadette, Dieckmann Karin, Bago-Horvath Zsuzsanna, Haslacher Helmuth, Widhalm Georg, Ilhan-Mutlu Aysegül, Minichsdorfer Christoph, Fuereder Thorsten, Szekeres Thomas, Oehler Leopold, Gruenberger Birgit, Pfeiler Georg, Singer Christian, Weltermann Ansgar, Berchtold Luzia, Preusser Matthias
Аннотация
BACKGROUND: Brain metastases (BM) are a devastating complication of HER2-positive metastatic breast cancer (BC) and treatment strategies providing optimized local and systemic disease control are urgently required. The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) over trastuzumab emtansine but data regarding intracranial activity is limited. In the primary outcome analysis of TUXEDO-1, a high intracranial response rate (RR) was reported with T-DXd. Here, we report the final PFS and OS results.
PATIENTS AND METHODS: TUXEDO-1 accrued adult patients with HER2-positive BC and active BM (newly diagnosed or progressing) without indication for immediate local therapy. The primary endpoint was intracranial RR; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analyzed in the per-protocol population.
RESULTS: At 26.5 months median follow-up, median PFS was 21 months (95% CI: 13.3-n.r.) and median OS was not reached (95% CI: 22.2-n.r.). With longer follow-ups, no new safety signals were observed. The most common grade 3 adverse event was fatigue (20%). Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL was maintained over the treatment period.
CONCLUSIONS: T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive BC BM in line with results from the pivotal trials. These results support the concept of antibody-drug-conjugates as systemic therapy for active BM.
PATIENTS AND METHODS: TUXEDO-1 accrued adult patients with HER2-positive BC and active BM (newly diagnosed or progressing) without indication for immediate local therapy. The primary endpoint was intracranial RR; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analyzed in the per-protocol population.
RESULTS: At 26.5 months median follow-up, median PFS was 21 months (95% CI: 13.3-n.r.) and median OS was not reached (95% CI: 22.2-n.r.). With longer follow-ups, no new safety signals were observed. The most common grade 3 adverse event was fatigue (20%). Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL was maintained over the treatment period.
CONCLUSIONS: T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive BC BM in line with results from the pivotal trials. These results support the concept of antibody-drug-conjugates as systemic therapy for active BM.