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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
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FDA Approval Summary: Entrectinib for the Treatment of NTRK gene Fusion Solid Tumors

Leigh Marcus1, Martha Donoghue2, Stephanie Aungst2

  • 1Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. leigh.marcus@fda.hhs.gov.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|September 24, 2020
PubMed

Insights

Entrectinib is an FDA-approved cancer drug for solid tumors with NTRK gene fusions. It showed a 57% response rate in clinical trials, with manageable side effects.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare but actionable targets in various solid tumors.
  • Targeted therapies offer new treatment avenues for patients with specific genetic alterations.
  • The development of tissue-agnostic therapies broadens treatment options for rare cancers.

Purpose of the Study:

  • To summarize the FDA approval of entrectinib for NTRK fusion-positive solid tumors.
  • To present efficacy and safety data supporting entrectinib's use.
  • To highlight entrectinib as a biomarker-defined, tissue-agnostic cancer therapeutic.

Main Methods:

  • Review of clinical trial data supporting entrectinib's efficacy and safety.
  • Analysis of response rates, duration of response, and adverse events.
  • Assessment of patient population characteristics, including tumor types and metastatic status.

Main Results:

  • Entrectinib demonstrated a 57% overall response rate in 54 patients with NTRK fusion-positive solid tumors.
  • Responses were durable, with 68% lasting six months or longer.
  • Common serious toxicities included heart failure, CNS effects, and hepatotoxicity, which were manageable.

Conclusions:

  • Entrectinib is an effective and approved treatment for adult and pediatric patients with NTRK fusion-positive solid tumors.
  • The drug offers a tissue-agnostic, biomarker-driven approach to cancer therapy.
  • Adverse events associated with entrectinib are manageable through dose adjustments.

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