Systemic and Intracranial Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Mutant NSCLC Across Treatment Lines: Evidence From the TRACER/HERTras Real-World Cohort

作者：Oliver Illini, Anna-Carina Hund, Hans‐Georg Kopp, Mor Moskovitz, Giannis Mountzios, Wolfgang M. Brueckl, Martin Früh, Marie-Elisabeth Leßmann, Petros Christopoulos, Albrecht Stenzinger, Michael Thomas, Roni Gillis, Nir Peled, Fabian Acker, Alfredo Addeo, Andriani Charpidou, Christian Grohé, Horst-Dieter Hummel, Laetitia Mauti, Sacha I. Rothschild, Sabine Schmid, Christian Schumann, Damien Urban, Robert Wurm, Simon Ekman, Marcus Skribek, Franziska Glanemann, Marcel Wiesweg, Christoph Jakob Ackermann, Sofia Agelaki, Petra Hoffknecht, Marko Jakopović, Jens Kern, David König, Katharina Kostenzer, Cornelia Kropf-Sanchen, Eckart Laack, David Lang, Laurenz Nagl, Georg Pall, Martin Reck, Waleed Kian, Anna T. Allemann, Jürgen Alt, David Araújo, Hanibal Bohnenberger, Alexandros Bokas, Hannah Fabikan, Krainer-Jacobs Julie, Christoph Weinlinger, Adrianus Johannes de Langen, Evangelos Georgios Fergadis, Rieke Fischer, Elena Fountzilas, Patrizia Froesch, Nikolaj Frost, Frank Griesinger, Franziska Jordan, Charisios Karanikiotis, Barbara Kiesewetter, Ippokratis Korantzis, Andrea Lopes Machado, Panagiota Economopoulou, Arnold Pilz, Patrick Reimann, Achim Rittmeyer, Akram Saad, Konstantinos Samitas, Karsten Schulmann, Riyaz Shah, Jan Alexander Stratmann, Hossein Taghizadeh, Kai Tammoscheit, Amanda Tufman, Jan-Phillip Weber, Ewald Wöll, Arschang Valipour, Tobias R. Overbeck, Maximilian J. Hochmair · 发表于：Journal of Thoracic Oncology · 年份：2026 · DOI：10.1016/j.jtho.2026.103651 · 被引用次数：3 · 研究领域：Lung Cancer Treatments and Mutations、HER2/EGFR in Cancer Research、Lung Cancer Research Studies

INTRODUCTION: HER2 mutations define a distinct, therapeutically actionable subset of NSCLC. Trastuzumab deruxtecan (T-DXd) has demonstrated strong activity in clinical trials, but real-world data are limited. METHODS: We conducted a retrospective, multinational cohort study of patients with advanced HER2-mutant NSCLC treated with T-DXd outside clinical trials between August 2021 and January 2025 across 68 centers in Europe and Israel. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), intracranial efficacy, and safety. RESULTS: Among 168 patients (median age 62 y; 59% female; 56% never-smokers), the ORR was 54.8% (95% confidence interval [CI]: 46.9-62.4) and disease control rate was 88.7% (95% CI: 82.9-93.1). Median PFS was 7.2 months (95% CI: 6.2-9.7) and median OS was 18.3 months (95% CI: 13.3-24.8). Treatment-naive patients (n = 18) achieved an ORR of 72.2% (95% CI: 46.5-90.3) and a median OS of 22.1 months (95% CI: 10.0-not evaluable). Patients with measurable brain metastases (n = 27) had an intracranial ORR of 74.1% (95% CI: 53.7-88.9), including 25.9% complete responses. Grade 3 or higher treatment-related adverse events occurred in 32% of patients. Interstitial lung disease/pneumonitis occurred in 14% (four fatal cases) of patients, without consistent predictors. CONCLUSIONS: In the largest real-world cohort reported to date, T-DXd demonstrated robust systemic and intracranial ...