Systemic and Intracranial Efficacy and Safety of Trastuzumab Deruxtecan in Patients with HER2-Mutant Non-Small Cell Lung Cancer across Treatment Lines: Evidence from the TRACER/HERTras Real-World Cohort.

Introduction HER2 mutations define a distinct, therapeutically actionable subset of non-small cell lung cancer (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 endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), intracranial efficacy, and safety. Results Among 168 patients (median age 62 years; 59% female; 56% never-smokers), the ORR was 54.8% (95%CI, 46.9-62.4) and disease control rate 88.7% (95%CI, 82.9-93.1). Median PFS was 7.2 months (95%CI, 6.2-9.7) and OS 18.3 months (95%CI, 13.3-24.8). Treatment-naïve patients (n=18) achieved an ORR of 72.2% (95%CI, 46.5-90.3) and median OS of 22.1 months (95%CI, 10.0-NE). 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 treatment-related adverse events occurred in 32% of patients. Interstitial lung disease (ILD)/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 activity in HER2-mutant NSCLC, including treatment-naïve patients and those with active brain metastases who were largely excluded from prior studies. Toxicity was consistent with previous reports, with ILD remaining the main safety concern. These findings support integration of HER2-targeted therapies into evolving treatment algorithms.

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Publication Details

Journal
Open Access CRIS of the University of Bern
Published
2026-02-24
DOI
https://doi.org/10.48620/95866
Primary Topic
Lung Cancer Treatments and Mutations
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article
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article

Systemic and Intracranial Efficacy and Safety of Trastuzumab Deruxtecan in Patients with HER2-Mutant Non-Small Cell Lung Cancer across Treatment Lines: Evidence from the TRACER/HERTras Real-World Cohort.

Panagiota Economopoulou, Charisios Karanikiotis, Maximilian J. Hochmair, Kai Tammoscheit et al.
Open Access CRIS of the University of Bern
Lung Cancer Treatments and Mutations
article

Systemic and Intracranial Efficacy and Safety of Trastuzumab Deruxtecan in Patients with HER2-Mutant Non-Small Cell Lung Cancer across Treatment Lines: Evidence from the TRACER/HERTras Real-World Cohort.

Panagiota Economopoulou, Charisios Karanikiotis, Maximilian J. Hochmair, Kai Tammoscheit, Hossein Taghizadeh, Alexandros Bokas, David König, Sofia Agelaki, Laurenz Nagl, A. de Langen, Anna Allemann, Christoph Ackermann, Marcus Skribek, Wolfgang M. Brueckl, Achim Rittmeyer, Robert Wurm, R. Shah, Jan Stratmann, Fabian Acker, Jens Kern, Oliver Illini, Ewald Wöll, Karsten Schulmann, Arnold Pilz, Patrick Reimann, N. Frost, Patrizia Froesch, Katharina Kostenzer, Sabine Schmid, Κonstantinos Samitas, Laetitia Mauti, Petra Hoffknecht, Franziska Jordan, Christoph Weinlinger, Eckart Laack, Elena Fountzilas, Franziska Glanemann, Damien Urban, Jürgen Alt, Jan-Phillip Weber, Mor Moskovitz, Hans-Georg Kopp, Alfredo Addeo, Roni Gillis, Nir Peled, Anna-Carina Hund, Fabikan Hannah, Krainer-Jacobs Julie, Akram Saad, Marie-Elisabeth Leßmann, Evangelos Georgios Fergadis, Waleed Kian, Martin Früh, Simon Ekman, Sacha I Rothschild, Arschang Valipour, Andriani Charpidou, Tobias R Overbeck, Petros Christopoulos, Giannis Mountzios, Ippokratis Korantzis, Cornelia Kropf-Sanchen, Christian Grohé, Frank Griesinger, David Araújo, Marcel Wiesweg, Albrecht Stenzinger, Georg Pall, Andrea Lopes Machado, Amanda Tufman, David Lang, Martin Reck, Michael Thomas
article en

Abstract

Introduction HER2 mutations define a distinct, therapeutically actionable subset of non-small cell lung cancer (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 endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), intracranial efficacy, and safety. Results Among 168 patients (median age 62 years; 59% female; 56% never-smokers), the ORR was 54.8% (95%CI, 46.9-62.4) and disease control rate 88.7% (95%CI, 82.9-93.1). Median PFS was 7.2 months (95%CI, 6.2-9.7) and OS 18.3 months (95%CI, 13.3-24.8). Treatment-naïve patients (n=18) achieved an ORR of 72.2% (95%CI, 46.5-90.3) and median OS of 22.1 months (95%CI, 10.0-NE). 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 treatment-related adverse events occurred in 32% of patients. Interstitial lung disease (ILD)/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 activity in HER2-mutant NSCLC, including treatment-naïve patients and those with active brain metastases who were largely excluded from prior studies. Toxicity was consistent with previous reports, with ILD remaining the main safety concern. These findings support integration of HER2-targeted therapies into evolving treatment algorithms.

Open Access CRIS of the University of Bern
Good health and well-being
Openalex Percentile: Top 37%
Lung Cancer Treatments and Mutations
DOIOpen Access PDFOpenAlex
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