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08-11-2023 | Trastuzumab Deruxtecan

Opportunities and Challenges for a Histology-Agnostic Utilization of Trastuzumab Deruxtecan

Authors: Niraj Neupane, Sangharsha Thapa, Abhinav Bhattarai, Kriti Ahuja, Ilana Schlam, Abhenil Mittal, Sara M. Tolaney, Paolo Tarantino

Published in: Current Oncology Reports | Issue 12/2023

Abstract

Purpose of Review

This review delves into the prospects and challenges offered by a potential pan-histological utilization of trastuzumab deruxtecan (T-DXd) in patients with advanced solid tumors.

Recent Findings

The HER2-targeted antibody-drug conjugate (ADC) T-DXd has shown broad activity across cancer types, with current indications for patients with biomarker-selected breast, gastric, and non-small-cell lung cancer and relevant activity observed in multiple histology-specific trials. Moreover, two recently reported phase 2 trials (DESTINY-Pantumor02 and HERALD) have supported the potential for a pan-cancer utilization of this ADC in patients with advanced cancers expressing HER2 or with HER2 amplifications.

Summary

By improving the delivery of cytotoxic chemotherapy, ADCs have allowed for meaningful clinical advantages in broad populations of cancer patients, often leading to survival advantages over conventional chemotherapy. Notably, the broad spectrum of activity of certain ADCs has led to the hypothesis of a histology-agnostic utilization based on detecting specific biomarkers, similar to what is already established for certain targeted treatments and immunotherapy. To date, T-DXd has shown the broadest activity across cancer types, with current approvals in breast, gastric, and lung cancer, and relevant antitumor activity observed in a multiplicity of additional cancer types. The optimization of the drug dose, identification of predictive biomarkers, and clarification of mechanisms of resistance will be critical steps in view of a pan-histological expansion in the use of T-DXd.

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Title: Opportunities and Challenges for a Histology-Agnostic Utilization of Trastuzumab Deruxtecan
Authors: Niraj Neupane
Sangharsha Thapa
Abhinav Bhattarai
Kriti Ahuja
Ilana Schlam
Abhenil Mittal
Sara M. Tolaney
Paolo Tarantino
Publication date: 08-11-2023
Publisher: Springer US
Keywords: Trastuzumab Deruxtecan
Solid Tumor
Breast Cancer
Breast Cancer
Biomarkers
Published in: Current Oncology Reports / Issue 12/2023
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI: https://doi.org/10.1007/s11912-023-01469-3

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