A randomized clinical study comparing trabectedin combined with regional hyperthermia with trabectedin in patients with advanced soft tissue sarcoma: HyperTET, a German Interdisciplinary Sarcoma Group trial

Schuebbe GE, Xu Y, Lindner LH, Di Gioia D, Abdel-Rahman S, Kunz WG, Roshchyna T, Fenderle R, Bücklein V, Reichardt P, Pink D, Flörcken A, Ott O, Fietkau R, Kampmann E, von Bergwelt-Baildon M, Kasper B, Issels R (2026)

Publication Type: Journal article

Publication year: 2026

Journal

ESMO Open BMJ Publishing Group

Book Volume: 11

Article Number: 106921

Journal Issue: 4

DOI: 10.1016/j.esmoop.2026.106921

Abstract

Background: The German Interdisciplinary Sarcoma Group (GISG) assessed efficacy and safety of trabectedin plus regional hyperthermia (Tr + RHT) versus trabectedin (Tr) in patients with advanced soft tissue sarcoma (STS). Patients and methods: In this randomized, open-label, multicenter study, adults with advanced STS who had progressed after at least one line of anthracycline-based chemotherapy or were unsuited for this treatment were enrolled. Patients were randomly assigned 1 : 1 to receive Tr + RHT or Tr every 3 weeks. Stratification factors included histological subtype, prior surgery (at any time), metastatic status, and Eastern Cooperative Oncology Group performance status. The primary endpoint was progression-free survival (PFS) analyzed in the intention-to-treat (ITT) population. Results: Between 19 December 2014 and 7 December 2021, 118 eligible patients from five GISG centers were allocated to Tr + RHT (n = 60) or Tr (n = 58). Patients received a median of three cycles [interquartile range (IQR) 2-6.2 cycles] in the Tr + RHT arm and four cycles (IQR 2-6 cycles) in the Tr arm. Median PFS was 3.0 months [95% confidence interval (CI) 2.5-5.0 months] with Tr + RHT versus 3.5 months (95% CI 2.8-5.9 months) with Tr (stratified HR 0.86, 95% CI 0.57-1.29, P = 0.459). In a Cox proportional hazards model, patients receiving five or more cycles showed a median PFS of 12.8 months (95% CI 9.8-21.0 months) with Tr + RHT versus 7.8 months (95% CI 6.0-12.6 months) with Tr (stratified HR 0.33, 95% CI 0.13-0.86, P = 0.023). Most commonly reported grade 3/4 treatment-related adverse events (AEs) were hematologic, hepatic, and infections. Treatment-related deaths were reported in three patients (5.3%) of the Tr arm. Conclusions: Adding RHT to trabectedin did not improve PFS. Although the study was negative, a post hoc exploratory analysis of the subgroup of patients receiving ≥5 cycles of Tr + RHT showed an improvement in PFS. The combination had a manageable safety profile, serving as the basis for a subsequent study on maintenance therapy with trabectedin or lurbinectedin plus RHT in advanced STS.

Authors with CRIS profile

Oliver Ott Department of Radiation Oncology Rainer Fietkau Lehrstuhl für Strahlentherapie

Involved external institutions

Klinikum der Universität München (LMU Klinikum) DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) HELIOS Kliniken DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) DE Germany (DE)

How to cite

APA:

Schuebbe, G.E., Xu, Y., Lindner, L.H., Di Gioia, D., Abdel-Rahman, S., Kunz, W.G.,... Issels, R. (2026). A randomized clinical study comparing trabectedin combined with regional hyperthermia with trabectedin in patients with advanced soft tissue sarcoma: HyperTET, a German Interdisciplinary Sarcoma Group trial. ESMO Open, 11(4). https://doi.org/10.1016/j.esmoop.2026.106921

MLA:

Schuebbe, G. E., et al. "A randomized clinical study comparing trabectedin combined with regional hyperthermia with trabectedin in patients with advanced soft tissue sarcoma: HyperTET, a German Interdisciplinary Sarcoma Group trial." ESMO Open 11.4 (2026).

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