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Selpercatinib versus multi-kinase inhibitors for advanced medullary thyroid cancer: A network meta-analysis of

Jiazhong Wang1, Gang Cao1, Yang Liu1

  • 1Department of Thyroid Surgery, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.

Frontiers in Endocrinology
|July 13, 2026
PubMed
Abstract

Insights

Selpercatinib shows superior efficacy and safety for advanced medullary thyroid cancer (MTC) compared to multi-kinase inhibitors (MKIs). This study highlights selpercatinib as a potential first-line treatment option for advanced MTC patients.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Advanced medullary thyroid cancer (MTC) treatment options include RET-targeted agents like selective RET inhibitors (SRIs) and multi-kinase inhibitors (MKIs).
  • Direct comparative efficacy and safety data for these agents are limited.
  • This study addresses the need for comparative analysis via network meta-analysis (NMA).

Purpose of the Study:

  • To evaluate and compare the relative efficacy and safety of RET-targeted therapies for advanced MTC.
  • To identify the optimal treatment strategy based on available clinical trial data.
  • To provide evidence-based recommendations for clinical practice.

Main Methods:

  • Systematic literature search of multiple databases (PubMed, Embase, Cochrane, Web of Science, CNKI) up to March 2026.
  • Inclusion of randomized controlled trials (RCTs) evaluating RET-targeted therapies in advanced MTC.
  • Network meta-analysis (NMA) using a frequentist random-effects model to compare progression-free survival (PFS), objective response rate (ORR), and ≥Grade 3 adverse events (AEs).

Main Results:

  • Selpercatinib demonstrated superior PFS (HR=0.10) and ORR (OR=122.6) compared to cabozantinib and vandetanib.
  • Selpercatinib showed a favorable safety profile with no significant increase in ≥Grade 3 AEs versus placebo (OR=1.34).
  • Anlotinib exhibited the highest toxicity (OR=12.00), while selpercatinib avoided common MKI off-target toxicities like hypertension and diarrhea, despite some hepatotoxicity (OR=4.20).

Conclusions:

  • Selpercatinib exhibits superior efficacy (PFS, ORR) and a more favorable safety profile for advanced MTC compared to MKIs.
  • Results support selpercatinib as a recommended first-line option for advanced MTC.
  • Caution is advised due to population heterogeneity; individualized treatment decisions are recommended.
Keywords:
RET inhibitorsmedullary thyroid cancermulti-kinase inhibitorsnetwork meta-analysisselpercatinib

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