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HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01

Author

Listed:
  • Salvatore Siena

    (Grande Ospedale Metropolitano Niguarda)

  • Kanwal Raghav

    (The University of Texas MD Anderson Cancer Center)

  • Toshiki Masuishi

    (Aichi Cancer Center Hospital)

  • Kensei Yamaguchi

    (The Cancer Institute Hospital of JFCR)

  • Tomohiro Nishina

    (National Hospital Organization Shikoku Cancer Center)

  • Elena Elez

    (Universitat Autònoma de Barcelona)

  • Javier Rodriguez

    (Clinica Universidad de Navarra)

  • Ian Chau

    (Royal Marsden NHS Foundation Trust)

  • Maria Bartolomeo

    (Fondazione IRCCS Istituto Nazionale Tumori)

  • Hisato Kawakami

    (Kindai University Hospital)

  • Fumitaka Suto

    (Daiichi Sankyo)

  • Makito Koga

    (Ltd)

  • Koichiro Inaki

    (Ltd)

  • Yusuke Kuwahara

    (Daiichi Sankyo)

  • Issey Takehara

    (Ltd)

  • Daniel Barrios

    (Daiichi Sankyo)

  • Kojiro Kobayashi

    (Daiichi Sankyo)

  • Axel Grothey

    (West Cancer Center)

  • Takayuki Yoshino

    (National Cancer Center Hospital East)

Abstract

DESTINY-CRC01 (NCT03384940) was a multicentre, open-label, phase 2 study that investigated the safety and efficacy of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-expressing metastatic colorectal cancer (CRC). The present exploratory biomarker analysis aims to investigate relationships between biomarkers and clinical outcomes in patients with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+ and in situ hybridization [ISH] positive) Cohort A (N = 53) of DESTINY-CRC01. Higher levels of HER2 biomarkers in baseline tissue and liquid biopsies, including HER2 status (IHC/ISH), HER2/CEP17 ratio, HER2 ISH signals, HER2 H-score, plasma HER2 (ERBB2) amplification status, HER2 adjusted plasma copy number, and HER2 extracellular domain correlate with antitumor activity (indicated by objective response rate, progression-free survival, and overall survival) of T-DXd. Baseline circulating tumor DNA (ctDNA) analysis suggests antitumor activity of T-DXd in patients who had baseline activating RAS, PIK3CA, or HER2 mutations detected in ctDNA.

Suggested Citation

  • Salvatore Siena & Kanwal Raghav & Toshiki Masuishi & Kensei Yamaguchi & Tomohiro Nishina & Elena Elez & Javier Rodriguez & Ian Chau & Maria Bartolomeo & Hisato Kawakami & Fumitaka Suto & Makito Koga &, 2024. "HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53223-3
    DOI: 10.1038/s41467-024-53223-3
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    References listed on IDEAS

    as
    1. Takayuki Yoshino & Maria Bartolomeo & Kanwal Raghav & Toshiki Masuishi & Fotios Loupakis & Hisato Kawakami & Kensei Yamaguchi & Tomohiro Nishina & Zev Wainberg & Elena Elez & Javier Rodriguez & Marwan, 2023. "Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Sandra Misale & Rona Yaeger & Sebastijan Hobor & Elisa Scala & Manickam Janakiraman & David Liska & Emanuele Valtorta & Roberta Schiavo & Michela Buscarino & Giulia Siravegna & Katia Bencardino & Andr, 2012. "Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer," Nature, Nature, vol. 486(7404), pages 532-536, June.
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