Treatment of Advanced or Metastatic NSCLC with RET Gene Fusion

Advanced or metastatic non-small cell lung cancer (NSCLC) harboring a RET gene fusion defines a molecularly distinct subgroup that warrants a targeted treatment strategy. Identifying this alteration at diagnosis is essential to selecting the appropriate first-line approach.

Clinical Scenario

RET gene fusions occur in approximately 1–2% of patients with NSCLC and are more common in adenocarcinoma histology. Importantly, the presence of a RET gene fusion — regardless of fusion partner — is associated with responsiveness to oral RET-directed targeted kinase inhibitors.

Treatment Approach — Partial Overview

First-line targeted therapy is recommended for patients with advanced or metastatic NSCLC and a confirmed RET gene fusion, with specific preferred oral agents established for this molecular subtype.

Full regimen details — preferred agents, sequencing, and eligibility criteria — are available in the structured protocol below.

Instant Access to Structured Evidence-Based Regimens

References

RET gene fusions occur in about 1% to 2% of patients with NSCLC and are more frequent in patients with adenocarcinoma histology.

The presence of a RET gene fusion is associated with responsiveness to oral RET TKIs regardless of fusion partner.

The Panel recommends pralsetinib or selpercatinib as preferred first-line therapy options for patients with advanced or metastatic NSCLC and RET gene fusion; both are appropriate for a PS of 0–4.

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