Efficacy and Safety of RET-Specific Kinase Inhibitors in RET-Altered Cancers: A Systematic Review

Cancer Invest. 2023 Sep;41(8):739-749. doi: 10.1080/07357907.2023.2255655. Epub 2023 Oct 31.

Abstract

RET proto-oncogene encodes receptor tyrosine kinase. Selpercatinib and pralsetinib are the only RET-specific tyrosine kinase inhibitors approved by FDA in RET-altered tumors. We searched PubMed, Embase, Cochrane, WOS, and Clinicaltrials.gov. Objective-response, complete-response, and partial-response were 60-89%, 0-11%, and 55-89%, respectively, with the use of RET-specific drugs. ≥Grade 3 adverse events were seen in 28-53% of the patients, with hypertension, change in ALT, QT prolongation, neutropenia, and pneumonitis among the common side effects. Hence, selpercatinib and pralsetinib were effective and well tolerated by most of the patients with RET-altered tumors.

Keywords: RET-inhibitor; RET-mutation; Selpercatinib; lung cancer; meta-analysis; systematic review; thyroid cancer.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Hypertension*
  • Lung Neoplasms*
  • Neoplasms* / drug therapy
  • Neutropenia*
  • Protein Kinase Inhibitors / adverse effects
  • Proto-Oncogene Proteins c-ret / genetics

Substances

  • Protein Kinase Inhibitors
  • RET protein, human
  • Proto-Oncogene Proteins c-ret