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Novel HER2-Directed Treatments in Advanced Gastric Carcinoma: AnotHER Paradigm Shift?

Angela Dalia Ricci1,2, Alessandro Rizzo1,2, Fabiola Lorena Rojas Llimpe1

  • 1Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.

Cancers
|April 30, 2021
PubMed

Insights

Human epidermal growth factor receptor 2 (HER2) is a target in gastric adenocarcinoma (GC). Newer treatments like trastuzumab deruxtecan show promise for HER2-positive GC patients, expanding therapeutic options.

Area of Science:

  • Oncology
  • Gastroenterology
  • Pharmacology

Background:

  • Human epidermal growth factor receptor 2 (HER2) overexpression/amplification occurs in 15-20% of gastric adenocarcinoma (GC) cases.
  • Trastuzumab plus chemotherapy was the standard first-line treatment for HER2-positive advanced GC since the ToGA trial (2010).
  • Not all HER2-positive GC patients benefit from current targeted therapies, and subsequent studies have yielded mixed results.

Purpose of the Study:

  • To review current HER2-targeted treatments for advanced gastric adenocarcinoma.
  • To focus on emerging novel HER2-directed therapies and future research directions in GC treatment.

Main Methods:

  • Review of clinical trial data and literature on HER2-targeted therapies in gastric adenocarcinoma.
  • Analysis of recent advancements, including trastuzumab deruxtecan (T-DXd) and its approval status.
  • Discussion of treatment outcomes and patient benefit in the context of HER2 status.

Main Results:

  • Trastuzumab deruxtecan (T-DXd) received FDA approval in January 2021 for pre-treated, unresectable, locally advanced, or metastatic HER2-positive GC.
  • The DESTINY-Gastric01 study demonstrated efficacy for T-DXd in this patient population.
  • Ongoing research explores new HER2-directed agents and strategies for GC.

Conclusions:

  • HER2-targeted therapies continue to evolve for advanced gastric adenocarcinoma.
  • Trastuzumab deruxtecan represents a significant advancement for a subset of HER2-positive GC patients.
  • Future research is crucial to optimize HER2-directed treatment strategies and improve outcomes in GC.
Keywords:
ErbB2HER2gastric cancertrastuzumabtrastuzumab deruxtecan

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