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Investigational multitargeted kinase inhibitors in development for head and neck neoplasms

Ana Marija Sola1, Daniel E Johnson1, Jennifer R Grandis1

  • 1a Department of Otolaryngology - Head and Neck Surgery , University of California , San Francisco , CA , USA.

Expert Opinion on Investigational Drugs
|February 13, 2019
PubMed
Abstract

Insights

Multitargeted tyrosine kinase inhibitors (m-TKIs) show promise for head and neck squamous cell carcinoma (HNSCC) treatment. Combining m-TKIs with other therapies or using them in specific patient subgroups may improve outcomes.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Head and neck squamous cell carcinoma (HNSCC) survival rates remain poor despite current treatments.
  • Existing therapies like chemotherapy and radiation have significant toxicities.
  • Novel targeted therapies, including epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint inhibitors, offer modest survival benefits with improved toxicity profiles.

Purpose of the Study:

  • To review early-stage investigations of multitargeted tyrosine kinase inhibitors (m-TKIs) for HNSCC.
  • To evaluate the efficacy of m-TKIs in preclinical and early clinical trials.
  • To identify potential biomarkers and combination therapy strategies for m-TKIs in HNSCC.

Main Methods:

  • Literature review of preclinical studies and early-phase clinical trials involving m-TKIs for HNSCC.
  • Evaluation of efficacy data, biomarker identification, and combination therapy potential.
  • Analysis of resistance mechanisms and predictive biomarkers for m-TKI response.

Main Results:

  • Single-agent m-TKIs have shown limited efficacy in unselected HNSCC populations.
  • Most promising results observed when m-TKIs are combined with other therapies, such as immunotherapy.
  • Efficacy is enhanced in specific mutation-defined patient subgroups.

Conclusions:

  • m-TKIs represent a promising class of agents for HNSCC treatment.
  • Combination strategies and targeted patient selection are crucial for maximizing m-TKI efficacy.
  • Further research is needed to identify predictive biomarkers and overcome resistance mechanisms.
Keywords:
Head and neck cancerimmunotherapymultitargeted kinase inhibitorssquamous cell carcinomatyrosine-kinase inhibitors

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