Efficacy and Safety of targeted therapy Inhibitors for RET-driven Solid
Cancer: A Systematic Review and Meta-analysis
Abstract
Advanced and metastatic RET-driven solid cancer is not susceptible to
chemotherapy or radiotherapy. The development of targeted therapy has
led to a new therapeutic model. Nevertheless, no systematic evaluation
of their efficacy and safety has been carried out in RET-driven solid
cancer. Systematic review and single-arm meta-analysis were performed.
Four electronic databases were searched (PubMed, Embase, Cochrane
Library, and Web of Science) from each database’s inception date until
February 27, 2022. Study inclusion criteria focused on peer-reviewed
published articles that reported the efficacy and safety of targeted
therapy Inhibitors for RET-driven Solid Cancer, excluding case
reports/series, review papers, meta-analyses, organizational guidelines,
editorial letters, expert opinions, and conference abstracts. 15
randomized, locally advanced or metastatic RET-driven solid cancer
assays (n=1835) were included. Previously untreated with RET-Specific
Tyrosine Kinase Inhibitors(TKI) group showed the highest objective
remission rate(ORR) (0.75,95%CI=0.68-0.82) or disease control rate(DCR)
(0.96,95%CI=0.92-0.99), and lower dose reduction(34.8%) or
discontinuation(3.4%), but the performance of general adverse reactions
(Grade1-5 96.8%, Grade3-5 69.2%) were not as good as Multi-Target
Tyrosine Kinase Inhibitors (MKI) group, followed by previously
treated/untreated with MKI/TKI group (MIX group). Targeted therapy
inhibitors have significant efficacy in RET-driven solid cancer therapy.
The ORR, DCR parameters and adverse reaction of TKI are better than
those of MKI. It was also related to the patient’s previous treatment
status. The ORR/DCR of the patients who received no targeted therapy was
superior to those who received Vandetanib or Cabozantinib as first-line
therapy.