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Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.081
vdae090.081
Final Category: Novel Targets in CNS Metastases (Non-Immunologic)
AcademicSubjects/MED00300
AcademicSubjects/MED00310
NVTG-07 SAFETY, TOLERABILITY, AND ANTITUMOR ACTIVITY OF TRASTUZUMAB DERUXTECAN (T-DXD) IN PATIENTS WITH HER2+ METASTATIC BREAST CANCER (MBC) AND ACTIVE BRAIN METASTASES (BMS) IN DESTINY-BREAST07 (DB-07)
Anders Carey Duke Cancer Institute, Durham, NC, USA

Loi Sherene Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

Hamilton Erika Sarah Cannon Research Institute, Nashville, TN, USA

Jhaveri Komal Memorial Sloan Kettering Cancer Center, New York, NY, USA

Schmid Peter Barts Cancer Institute, Queen Mary University of London, London, United Kingdom

Gökmen Erhan Ege University Faculty of Medicine, Izmir, Turkey

Im Seock-Ah Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea, Republic of

Karaçin Cengiz Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey

Barrios Carlos Centro de Pesquisa em Oncologia, Hospital São Lucas, PUCRS, Porto Alegre, Brazil

Park Yeon Hee Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of

Topaloğlu Sernaz Trakya University Faculty of Medicine, Edirne, Turkey

Boston Sarice AstraZeneca, Gaithersburg, MD, USA

Konpa Adam AstraZeneca, Warsaw, Mazowieckie, Poland

Mondal Shoubhik AstraZeneca, Gaithersburg, MD, USA

André Fabrice Gustave Roussy, Paris-Saclay University, Villejuif, France

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i25i25
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

BACKGROUND

DEBBRAH, ROSET-BM, TUXEDO-1, and a pooled DB-01, -02, -03 analysis indicate robust efficacy of T-DXd in patients with stable/active BMs; however, efficacy in active BMs is not yet fully established. DB-07 is a Phase 1b/2, multicenter, open-label study exploring the safety, tolerability, and antitumor activity of T-DXd alone or in combination with other anticancer agents (NCT04538742). Results are from an interim analysis of the dose-expansion phase of T-DXd monotherapy in patients with active BMs.

METHODS

Patients had locally assessed HER2+ mBC with measurable disease. No or one prior line of therapy for mBC was allowed; a ≥12-month disease-free interval from (neo)adjuvant HER2-directed therapy or chemotherapy was required. Patients had untreated BMs not requiring local therapy or progressing BMs after local therapy. Ongoing use of systemic corticosteroids (>2 mg dexamethasone daily or equivalent) for control of BMs symptoms was exclusionary. Patients received T-DXd 5.4 mg/kg intravenously every 3 weeks. Primary objectives were safety and tolerability; additional endpoints included objective response rate (ORR) and progression-free survival (PFS) per RECIST 1.1 and Response Assessment in Neuro-Oncology (RANO)-BM.

RESULTS

Thirty-five patients with active BMs were treated. As of August 1, 2023, median follow up was 11.5 months (range 5.3–24.6). The most common any-grade adverse events (AEs) were nausea (74.3%; Grade 3, 5.7%) and vomiting (45.7%; Grade 3, 2.9%); AEs Grade ≥3 occurred in 18 patients (51.4%). By RECIST 1.1, confirmed ORR was 77.1% (80% CI 65.5, 86.2), and 12-month PFS rate was 84.5% (80% CI 74.1, 91.0). By RANO-BM, confirmed ORR was 57.1% (80% CI 44.9, 68.7) and 12-month PFS rate was 74.6% (80% CI 59.4, 84.8).

CONCLUSION

The safety profile is consistent with the known profile for T-DXd, and data confirm promising efficacy in patients with active BMs. Ongoing analyses will provide more mature data.
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pmc
