Advanced or Metastatic NSCLC with ROS1 Gene Fusion: Treatment After Progression
This protocol covers the management of advanced or metastatic non-small cell lung cancer (NSCLC) in patients with a confirmed ROS1 gene fusion — a molecularly defined subgroup that shapes both prognosis and treatment selection.
Clinical Scenario
ROS1 gene fusions occur in approximately 1–2% of patients with NSCLC. Their presence is associated with responsiveness to oral ROS1 tyrosine kinase inhibitors (TKIs), making molecular testing essential in this setting. This protocol addresses the advanced or metastatic stage, where systemic treatment decisions are guided by fusion status, prior therapy, and resistance profile.
Treatment Approach (Partial Overview)
For patients experiencing disease progression, subsequent targeted therapy options are available — including agents with activity against specific resistant mutations such as ROS1 G2032R. The selection between options is informed by mutation profile and prior treatment history.
The complete regimen, sequencing criteria, and full selection algorithm are available in the full protocol below.
References
- It is estimated that ROS1 gene fusions occur in about 1% to 2% of patients with NSCLC.
- The presence of a ROS1 gene fusion is associated with responsiveness to oral ROS1 TKIs.
- For asymptomatic progression on first-line targeted therapy, the Panel recommends repotrectinib, taletrectinib, or lorlatinib as subsequent therapy options, if not previously given.
- If a resistant mutation (such as ROS1 G2032R) is identified, then repotrectinib or taletrectinib are recommended treatment options.