Trastuzumab Deruxtecan in HER2-Expressing Digestive Cancers: A Retrospective Real-World Study from Institut Gustave Roussy

Abstract

Author(s): Chaymae CHBIHI*, Alice BOILEVE, Nouhaila CHAREF, Samia EL HAKYM, Hafssa EL HILALI, Sara NEJJARI, Abir OUFRID, Diango KEITA, Lamiae AMAADOUR, Karima OUALLA, Zineb BENBRAHIM, Samia ARIFI and Nawfel MELLAS

Background: Trastuzumab deruxtecan (T-DXd) is a HER2-targeting antibody-drug conjugate that has demonstrated significant efficacy in HER2-positive gastric cancer in clinical trials. However, real-world evidence across the broader spectrum of digestive malignancies remains limited. This study aimed to evaluate the effectiveness and safety of T-DXd in HER2-expressing digestive cancers in routine clinical practice. Methods: We conducted a retrospective, single-center study including 19 patients treated with T-DXd at Institut Gustave Roussy between January 2020 and June 2025. Eligible patients had HER2-positive digestive malignancies (IHC 3+ or IHC 2+/ ISH+). The primary endpoints were objective response rate (ORR) and progression- free survival (PFS). Secondary endpoints included overall survival (OS), disease control rate (DCR), and safety. Results: Gastric cancer was the most frequent primary site (78.9%), followed by esophageal (10.5%), biliary tract (5.3%) and pancreatic (5.3%). The ORR was 47.4% and the DCR was 63.2%. Median PFS was 4.21 months (95% CI: 1.51–6.67), and median OS was 4.76 months (95% CI: 1.51–6.67). HER2 status conversion was observed in 84.2% of patients. The most common adverse events were asthenia (73.7%), diarrhea (36.8%), and anemia (36.8%). Grade ≥3 adverse events included asthenia (9/19), diarrhea (3/19), and anemia (3/19). Interstitial lung disease occurred in 2 patients (10.5%), with one grade ≥3 event. Conclusion: In this real-world cohort of heavily pretreated patients with HER2- expressing digestive cancers, T-DXd demonstrated clinical activity consistent with pivotal trials, although with shorter survival due to the advanced disease context. The safety profile was manageable with appropriate monitoring, particularly for interstitial lung disease.

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