Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Sep 15;11(9):2538.
doi: 10.3390/biomedicines11092538.

The Safety Profiles of Two First-Generation NTRK Inhibitors: Analysis of Individual Case Safety Reports from the FDA Adverse Event Reporting System (FAERS) Database

Valerio Liguori  1   2 , Mario Gaio  1   2 , Alessia Zinzi  1   2 , Cecilia Cagnotta  1   2 , Consiglia Riccardi  1   2 , Giovanni Docimo  3 , Annalisa Capuano  1   2
Affiliations

The Safety Profiles of Two First-Generation NTRK Inhibitors: Analysis of Individual Case Safety Reports from the FDA Adverse Event Reporting System (FAERS) Database

Valerio Liguori et al. Biomedicines. .

Abstract

The first-generation tropomyosin receptor kinase (TRK) inhibitors, larotrectinib and entrectinib, represent exciting new developments in cancer treatment that offer relevant, rapid, and long-lasting clinical benefits. Larotrectinib and entrectinib are recommended as first-line treatments for locally advanced or metastatic non-small cell lung cancer (NSCLC) patients with positive TRK gene fusions. In this study, using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database between 2019 and 2022, a retrospective analysis was conducted to evaluate the safety profiles of these drugs. During our study period, 807 individual case safety reports (ICSRs) related to larotrectinib or entrectinib were retrieved from the FAERS database, of which 48.7% referred to females and 24.7% referred to adult patients (18-64 years) with a median age of 61.0 years. A total of 1728 adverse drug reactions (ADRs) were identified. The most frequently reported ADRs were dizziness and pain, which belong to the System Organ Classes (SOCs) "nervous system disorders" and "general disorders and administration site conditions". Regarding all ADRs, the median time to onset was 37.0 days for larotrectinib and 12.0 days for entrectinib. No evident safety concerns emerged in the long-term safety profiles (>365 days). Only 18 ICSRs were related to pediatric populations (≤16 years), of which 94.0% of the ICSRs were related to larotrectinib. The median age was 10.5 years, while most patients were female (44.4%). Our results show favorable risk-benefit profiles for larotrectinib and entrectinib. Considering the increased use of neurotrophic tyrosine receptor kinase (NTRK) inhibitors, continuous safety monitoring of larotrectinib and entrectinib is required for the detection of possible new adverse drug reactions.

Keywords: NTRK; TRK; agnostic drugs; entrectinib; larotrectinib; precision medicine.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of larotrectinib and entrectinib.
Figure 2
Figure 2
Distribution of the preferred term (PT) (at least accounted for ≥2% of all ADRs) related to each ADR reported in overall individual case safety Reports linked to larotrectinib (N = 832) and entrectinib (N = 896).
Figure 3
Figure 3
Boxplot of time to onset of ADRs after larotrectinib administration and after entrectinib administration. Time to onset is defined as the time in days from drug administration to the occurrence of an adverse event.
Figure 4
Figure 4
Distribution of the System Organ Class (SOC) related to each ADR reported in overall individual case safety reports linked to larotrectinib and/or entrectinib after 365 days.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Akhoon N. Precision Medicine: A New Paradigm in Therapeutics. Int. J. Prev. Med. 2021;12:12. - PMC - PubMed
    1. Tarantino P., Mazzarella L., Marra A., Trapani D., Curigliano G. The Evolving Paradigm of Biomarker Actionability: Histology-Agnosticism as a Spectrum, Rather than a Binary Quality. Cancer Treat. Rev. 2021;94:102169. doi: 10.1016/j.ctrv.2021.102169. - DOI - PubMed
    1. Adashek J.J., Subbiah V., Kurzrock R. From Tissue-Agnostic to N-of-One Therapies: (R) Evolution of the Precision Paradigm. Trends Cancer. 2021;7:15–28. doi: 10.1016/j.trecan.2020.08.009. - DOI - PubMed
    1. Lavacchi D., Roviello G., D’Angelo A. Tumor-Agnostic Treatment for Cancer: When How Is Better than Where. Clin. Drug Investig. 2020;40:519–527. doi: 10.1007/s40261-020-00915-5. - DOI - PubMed
    1. Flaherty K.T., Le D.T., Lemery S. Tissue-Agnostic Drug Development. Am. Soc. Clin. Oncol. Educ. Book Am. Soc. Clin. Oncol. Annu. Meet. 2017;37:222–230. doi: 10.1200/EDBK_173855. - DOI - PubMed

LinkOut - more resources