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Background <p>Molecular tumor boards (MTBs) are essential for selecting therapies for patients with rare and advanced cancers. We hypothesized that integrating biomarkers beyond targeted DNA/RNA next-generation sequencing (NGS) could increase actionable findings. Human epidermal growth factor receptor 2 (HER2)-low status has emerged as a critical biomarker in breast cancer, with potential relevance across other tumor types. Homologous recombination deficiency (HRD) is pivotal for the application of Poly(ADP-Ribose)-Polymerase (PARP) inhibitors in ovarian and breast cancer, although its role in other malignancies remains unclear. Antibody–drug conjugates (ADCs) are expanding precision oncology, with promising biomarkers like Trop-2, Nectin-4, and folate receptor alpha (FRα) showing potential across multiple tumor entities.</p> Methods <p>Tumors were analyzed using the TSO500® panel, enabling tumor mutational burden (TMB) readout. HER2 status was assessed via immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), alongside antibody–drug conjugate (ADC) IHC, microsatellite instability (MSI) polymerase chain reaction (PCR), mismatch repair (MMR) IHC, programmed death-ligand 1 (PD-L1) IHC, and HRD analysis. Cases were discussed weekly, and outcomes were systematically tracked. Data analysis evaluated the benefit of additional biomarker assessments.</p> Results <p>Among 658 patients, 329 received therapy recommendations, 182 based on supplementary biomarker analyses. One hundred recommendations were implemented, with 37% attributed to supplementary diagnostics. Among 64 response-evaluable patients, the clinical benefit rate (complete response + partial response + stable disease) was 45.3%. HER2-low status notably expanded targeted therapy options across tumor types, with similar implementation rates for HER2-low and HER2-amplified tumors. HRD analysis refined stratification in tumors with mutations in homologous recombination repair (HRR) genes beyond BRCA1/2, including PALB2, ATM, and CHEK2. ADC IHC supported 20 recommendations and two therapy implementations.</p> Conclusions <p>The integration of additional biomarker assessments into MTB workflows enhances precision oncology by expanding the pool of patients eligible for targeted therapies.</p>

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Supplementary biomarker testing in molecular tumor boards increases actionable therapy recommendations: a prospective real-world study of 658 patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月14日

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  • Alexander Scheiter,
  • Simon Mellin,
  • Felix Keil,
  • Johannes Meier,
  • Daniel Heudobler,
  • Christina Brummer,
  • Sabine Einhell,
  • Benjamin Zwicker,
  • Elena Wutzlhofer,
  • Frederik Hierl,
  • Sophie Klemm,
  • Elena Lüftl,
  • Tom Schneider,
  • Markus Perl,
  • Margit Klier-Richter,
  • Alexander Immel,
  • Till Kaltofen,
  • Matthias Grube,
  • Elisabeth Bumes,
  • Stephan Seitz,
  • Christian Schulz,
  • Sebastian Haferkamp,
  • Konstantin Drexler,
  • Anja Troeger,
  • Felix Steger,
  • Sophie Schlosser-Hupf,
  • Hauke Christian Tews,
  • Arne Kandulski,
  • Kristina Wohlfart,
  • Ramona Erber,
  • Ines Schönbuchner,
  • Davor Lessel,
  • Marco J. Schnabel,
  • Anja M. Sedlmeier,
  • Monika Klinkhammer-Schalke,
  • Julia Maurer,
  • Diego F. Calvisi,
  • Tobias Pukrop,
  • Ulrich Kaiser,
  • Daniela Hirsch,
  • Wolfgang Dietmaier,
  • Matthias Evert,
  • Florian Lüke,
  • Kirsten Utpatel

摘要

Background

Molecular tumor boards (MTBs) are essential for selecting therapies for patients with rare and advanced cancers. We hypothesized that integrating biomarkers beyond targeted DNA/RNA next-generation sequencing (NGS) could increase actionable findings. Human epidermal growth factor receptor 2 (HER2)-low status has emerged as a critical biomarker in breast cancer, with potential relevance across other tumor types. Homologous recombination deficiency (HRD) is pivotal for the application of Poly(ADP-Ribose)-Polymerase (PARP) inhibitors in ovarian and breast cancer, although its role in other malignancies remains unclear. Antibody–drug conjugates (ADCs) are expanding precision oncology, with promising biomarkers like Trop-2, Nectin-4, and folate receptor alpha (FRα) showing potential across multiple tumor entities.

Methods

Tumors were analyzed using the TSO500® panel, enabling tumor mutational burden (TMB) readout. HER2 status was assessed via immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), alongside antibody–drug conjugate (ADC) IHC, microsatellite instability (MSI) polymerase chain reaction (PCR), mismatch repair (MMR) IHC, programmed death-ligand 1 (PD-L1) IHC, and HRD analysis. Cases were discussed weekly, and outcomes were systematically tracked. Data analysis evaluated the benefit of additional biomarker assessments.

Results

Among 658 patients, 329 received therapy recommendations, 182 based on supplementary biomarker analyses. One hundred recommendations were implemented, with 37% attributed to supplementary diagnostics. Among 64 response-evaluable patients, the clinical benefit rate (complete response + partial response + stable disease) was 45.3%. HER2-low status notably expanded targeted therapy options across tumor types, with similar implementation rates for HER2-low and HER2-amplified tumors. HRD analysis refined stratification in tumors with mutations in homologous recombination repair (HRR) genes beyond BRCA1/2, including PALB2, ATM, and CHEK2. ADC IHC supported 20 recommendations and two therapy implementations.

Conclusions

The integration of additional biomarker assessments into MTB workflows enhances precision oncology by expanding the pool of patients eligible for targeted therapies.